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Clinical
Biomarkers Medicine
in
Periodontal Health
Covertemplate
and Disease
Subtitle forBenefits, and Future

Rationale,
Clinical Medicine Covers T3_HB
Directions
Second Edition
Nurcan Buduneli
1123
3
2
Biomarkers in Periodontal
Health and Disease
Nurcan Buduneli
Biomarkers in
Periodontal Health
and Disease
Rationale, Benefits,
and Future Directions
Nurcan Buduneli
Department of Periodontology
Faculty of Dentistry
Ege University
Izmir, Turkey
ISBN 978-3-030-37315-3 ISBN 978-3-030-37317-7 (eBook)

https://doi.org/10.1007/978-3-030-37317-7
© Springer Nature Switzerland AG 2020

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
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The supreme guide in life is science.
Do not be afraid of telling the truth.
Mustafa Kemal ATATÜRK
Dedicated to mom, who has always been the major
encouraging power behind me; to dad, who had always
believed in me
And to my dear daughter and son, who are my hope
for the future
Preface
Periodontal diseases continue to be one of the most common chronic infec-

tious and inflammatory diseases in the world. Pathogenic mechanisms acting
in periodontal diseases contain two major arms: the microbial component and
the host response. Knowledge on both aspects has been increasing tremen-
dously during the last two decades. Indeed, the progress in knowledge and the
available evidence have led European Federation of Periodontology and
American Academy of Periodontology to combine power and build up a new
classification system for periodontal diseases in 2017 after 18 years passed
since the 1999 Classification.
Periodontology is one of the most glamorous fields of dentistry with doz-
ens of exciting papers, which open up completely novel pathways of research.
“The more we understand the scenario the more complex it becomes.” This is
quite true for periodontology. However, this complexity not only attracts even
more scientists to work in this field but also stimulates building new bridges
between various disciplines of dentistry and medicine to make the story clear.
Development of chair-side diagnostic tests for determining the presence or
absence of periodontal disease and activity is still a challenge in periodontol-
ogy. The use of biofluid samples such as gingival crevicular fluid, whole
saliva, and serum as a means of evaluating host-derived products, as well as
exogenous components has a great potential for diagnosis and monitorisation
of periodontal diseases. Having more precise and early diagnostic tools may
enable early intervention and help to develop individually tailored treatment
modalities. We are not there, yet, but shall expect to arrive soon. The techno-
logical developments in laboratory methods and the closer collaboration with
different branches of medicine bring great hope for the future. The spirit of
positivity with “can do” and “will do” is definitely encouraging; however, it
is clear that reliable biomarkers should base on strong evidence. I hope this
monograph will help to fire more researchers working in the field of peri-
odontology to get involved.
Moonlight floods the whole sky from horizon to horizon
How much it can fill your room depends on its windows.
Mawlana Jalal-al-Din Rumi
İzmir, Anatolia Nurcan Buduneli

September 2019
ix
Acknowledgements
I am grateful to Dr. Burcu Kanmaz for kindly preparing all the illustrations
and providing the photographs for this book.
xi
Contents
1 Anatomy of Periodontal Tissues �� 1

1.1 Healthy Periodontal Tissues�� 1
1.1.1 Gingiva�� 1
1.1.2 Dentogingival Junction �� 2
1.1.3 Cementum �� 3
1.1.4 Periodontal Ligament�� 4
1.1.5 Alveolar Bone �� 5
1.2 Blood Supply of the Periodontium �� 6
1.3 Lymphatic System of the Periodontium�� 6
1.4 Nerves of the Periodontium�� 6
1.5 Stem Cells of the Periodontium�� 6
References�� 7
2 Nature of Periodontal Diseases �� 9
2.1 Inflammation �� 9
2.2 Pathogen Microorganisms�� 11
2.3 Immune Response�� 14
2.4 Osteoclastic Bone Resorption �� 15
2.5 Network of Cytokines and Chemokines �� 15
2.6 Lipid Mediators of Inflammation�� 16
2.7 Conclusion�� 17
References�� 17
3 Conventional Diagnosis of Periodontal Diseases
and the 2017 Classification System�� 21
3.1 1989 Classification of Periodontal Diseases �� 21
3.2 1999 Classification of Periodontal Disease�� 22
3.3 2017 Classification of Periodontal Diseases �� 22
3.4 Medical and Dental History�� 25
3.5 Clinical Periodontal Parameters�� 26
3.5.1 Bleeding on Probing �� 29
3.5.2 Suppuration �� 29
3.5.3 Clinical Attachment Level�� 30
3.5.4 Relative Attachment Level�� 30
3.5.5 Probing Depth �� 30
3.5.6 Gingival Recession �� 31
3.5.7 Furcation Lesions�� 31
3.5.8 Pathologic Tooth Migration�� 31
xiii
xiv Contents
3.5.9 Increased Tooth Mobility�� 31

3.5.10 Bone Sounding�� 32
3.5.11 Oral Hygiene Status�� 32
3.6 Radiographical Evaluation�� 32
3.7 Limitations of the Conventional Diagnostic Methods�� 33
References�� 34
4 Novel Diagnostic Approaches in Periodontics �� 35
4.1 Controlled-Force, Standardised Probes�� 36
4.2 Voice-Activated Charting System �� 36
4.3 Advanced Techniques with 3-Dimensional Imaging�� 36
4.4 Computer-Assisted Digital Radiography�� 37
4.5 Computer-Assisted Densitometric Image Analysis (CADIA)�� 37
4.6 Cone-Beam Computerised Tomography�� 37
References�� 39
5 Biomarkers for Periodontal Diseases �� 41
5.1 Main Text�� 41
5.1.1 How to Find a Needle in the Haystack?�� 41
5.2 Microbial Factors for the Diagnosis of Periodontal Diseases�� 42
5.3 Biomarkers for Detection of Periodontal Disease�� 43
5.4 Biomarkers for Prognosis of Non-surgical
Periodontal Treatment�� 49
5.5 Biomarkers for Monitoring of Disease Progress�� 50
5.5.1 Response to Treatment�� 50
5.6 Point-of-Care Diagnostics�� 53
5.7 Limitations of Available Studies �� 53
References�� 55
6 Biological Samples for Biomarkers: Strengths
and Weaknesses�� 59
6.1 Saliva�� 59
6.1.1 Collection of Saliva Samples�� 60
6.1.2 Content of Saliva�� 61
6.1.3 Functions of Saliva�� 61
6.2 Gingival Crevicular Fluid�� 62
6.2.1 Methods of Collection�� 63
6.2.2 Reporting GCF Sample Volume and Biomarker Data�� 65
6.3 Serum or Plasma �� 66
6.4 Gingival Tissue Biopsy �� 66
6.5 Calcified Tissue Biopsy�� 67
6.6 Plaque�� 67
References�� 67
7 Technologies for Biomarkers in Periodontics�� 69
7.1 Biochemical Analyses�� 69
Contents xv
7.1.1 Point-of-Care Diagnostics�� 70

7.1.2 Lab-on-a-Chip Methods�� 71
7.1.3 Proteomic Analysis �� 71
7.1.4 Mass Spectrometry (MS)�� 72
7.1.5 Shotgun Proteomics�� 72
7.1.6 Gel Electrophoresis�� 73
7.1.7 Genetics and Periodontal Diagnosis �� 73
7.1.8 Epigenetics�� 73
7.1.9 Transcriptomics�� 74
7.1.10 Metabolomics�� 74
7.2 Microbiological Laboratory Analyses�� 75
7.2.1 Culture Technique �� 75
7.2.2 Polymerase Chain Reaction (PCR)�� 76
7.2.3 Checkerboard DNA–DNA Hybridisation �� 76
References�� 77
8 Biomarkers in Periodontal Disease and Systemic
Health Intersection�� 79
8.1 What Is a Biomarker? �� 80
8.2 Systemic Biomarkers in Saliva �� 80
8.3 Systemic Biomarkers in Circulation �� 81
8.4 Systemic Biomarkers in Association
with Systemic Diseases�� 82
8.5 Limitations of Systemic Biomarkers
as Periodontal Diagnostics�� 83
References�� 84
9 Past, Present, and Future of Periodontics�� 87
9.1 Past�� 87
9.2 Present�� 88
9.3 Future�� 88
References�� 90
Anatomy of Periodontal Tissues
1
Periodontal tissues comprise both soft and hard the architecture of (human) tissues is necessary
tissues and have unique features as such soft tis- to enable a creative mind to ask pertinent biologi-
sues are in close contact with the calcified tissues cal questions” (Schroeder 1997).
and there is always a biofilm around. The peri-
odontium comprises four distinguished tissues
gingiva, root cementum, periodontal ligament, 1.1 Healthy Periodontal Tissues
and alveolar bone (Fig. 1.1). Altogether these
tissues function as tooth supporting organ sys- 1.1.1 Gingiva
tem and their severe destruction can lead tooth
loss. The extracellular matrix of each periodon- The gingiva is divided anatomically into mar-
tal tissue has fibrous and nonfibrous elements ginal, attached, and interdental gingiva. The mar-
including collagens, elastin, fibronectin, laminin, ginal or unattached gingiva is the terminal border
osteopontin, bone sialoprotein, growth factors, of the gingiva surrounding the teeth in collar-like
proteoglycans, lipids, minerals, and water. The fashion. The free gingival groove is the border
interactions between these components not only between the marginal and attached gingiva and
determine tissue health, but are also involved in visible in approximately half of the cases. The
tissue damage, repair, and regeneration. Tooth marginal gingiva is the soft tissue wall of the gin-
loss means loss of vital functions such as bit- gival sulcus, it is about 1 mm wide in normal and
ing, chewing, speech, and aesthetics eventu- healthy periodontium and can be separated from
ally causing decreased self-esteem as well as the tooth surface with a periodontal probe.
social problems. The primary aetiological factor The gingival sulcus is the shallow crevice
for periodontal diseases is the microbial dental around the tooth bounded by the tooth surface
plaque or the oral biofilm. The microorganisms in on one side and by the marginal gingiva on the
the biofilm trigger host response and the activated other (Fig. 1.1). The clinical determination of the
inflammatory, immune cells cause tissue destruc- depth of gingival sulcus is an important diagnos-
tion. For successful periodontal treatment, it is tic parameter. The clinically healthy gingiva has
imperative to clarify the disease causing agents a sulcus depth of 1–3 mm.
together with the disease modifying factors. On The attached gingiva is continuous with the
the other hand, understanding the physiology of marginal gingiva and it is firm, resilient, and
periodontal tissues is of utmost importance to tightly bound to the underlying periosteum of
develop protective strategies as well as new treat- alveolar bone. The width of attached gingiva
ment modalities. Schroeder stated, “Insight into is an important clinical parameter, extending
© Springer Nature Switzerland AG 2020 1

N. Buduneli, Biomarkers in Periodontal Health and Disease,
https://doi.org/10.1007/978-3-030-37317-7_1
2 1 Anatomy of Periodontal Tissues
Fig. 1.1 Anatomy of

the periodontal tissues
Enamel
Sulcular epithelium
Gingival sulcus
Oral epithelium
Junctional epithelium
Cementoemanel junction
Supra-alveolar connective tissue
Dentin
Periodontal ligament
Cementum
Alveolar bone
between the mucogingival junction and the pro-

jection on the external surface of the bottom of
the gingival sulcus or periodontal pocket. The
width of attached gingiva is greatest in the inci-
sor region (3.5–4.5 mm in the maxilla and 3.3–
3.9 mm in the mandible) and less in the posterior
region, with the least width in the first premolar
area (1.9 mm in the maxilla and 1.8 mm in the Fig. 1.2 Pristine healthy periodontal tissues
mandible).
Interdental gingiva normally occupies the gin-
gival embrasure, which is the interproximal space 1.1.2 Dentogingival Junction
beneath the area of tooth contact. Figure 1.2
shows an example of pristine healthy periodon- The dentogingival junction is the term to define
tium. It can be pyramidal or have a “col” shape. the gingival portion facing the tooth surface and
The shape of the interdental gingiva depends comprises both epithelial and connective tissue
on the contact point between the two adjacent components. The epithelium has three compo-
teeth. Presence or absence of gingival recession nents; gingival, sulcular, and junctional epithelium.
or hyperplasia directly affects the dimension and Among these functional compartments, the junc-
shape of the interdental gingiva. tional epithelium has very unique characteristics
1.1 Healthy Periodontal Tissues 3
as it faces the calcified tooth surface and seals migrate from the vessels in the connective tis-
off periodontal tissues from the oral cavity. sue reaching out the gingival sulcus. The nature
Therefore, it has to be intact in order to be able to of the connective tissue beneath an epithelium
protect deeper tissues from the microbiological, has a determining role on the character of the
chemical, or physical inflammatory factors origi- epithelium. The subepithelial connective tis-
nating from the oral environment. The structural sue provides instructive signals for the normal
and functional uniqueness of the junctional epi- progression of the stratified squamous epithelia
thelium makes it a very efficient barrier against (Karring et al. 1971, 1975). The connective tissue
periodontal pathogens and their virulence factors. immediately subjacent to the epithelium is rich in
The junctional epithelium originates from type I and type III collagen and also small pro-
the reduced enamel epithelium during the tooth teoglycans decorin and biglycan. The basement
eruption into the oral cavity. It is located around membranes at the junctions of connective tissue
the cervical portion of the tooth as a collar at with epithelium and cementum, the rete pegs, and
the level of cementoenamel junction (CEJ). It the connective tissue around the blood vessels
constitutes the base of the gingival sulcus. It is and nerves contain high amount of collagen type
non-differentiated, stratified squamous epithe- IV (Chavrier et al. 1984; Narayanan et al. 1985;
lium and has a very high rate of cell turnover. It Romanos et al. 1991).
is thickest near the bottom of the gingival sulcus
and ends with a few cells along the tooth sur-
face. The epithelial attachment consists of a basal 1.1.3 Cementum
lamina-like structure that is adherent to the tooth
surface that is a specialised extracellular matrix, Cementum is the calcified avascular connective
which is rich in glycoconjugates. It also contains tissue that covers the roots of the teeth and is the
laminin 5, which mediates adhesion and migra- periodontal tissue where the principal periodontal
tion of keratinocytes (Frank and Carter 2004). ligament fibres are attached. The ultrastructure of
The junctional epithelium cells contain fewer cementum is similar to that of bone and dentin
tonofilaments and desmosomes, and wider (Selvig 1965). Basically, there are two types of
intercellular spaces compared to the gingival cementum in regard with the presence or absence
epithelium. These wide spaces contain polymor- of cellular component and the origin of the col-
phonuclear leukocytes (PNL) and monocytes that lagen fibres of the extracellular matrix; acellular
originate from the subepithelial connective tissue extrinsic fibre cementum and cellular intrinsic
and migrate into the gingival sulcus. Together fibre cementum.
with their enzymes these cells are the first line Acellular extrinsic fibre cementum, which
of defence against the microbial attacks from the is also called primary cementum or acellular
oral biofilm. These cells can secrete molecules cementum, exists on the cervical half to two
such as alpha (α)- and beta (β)-defensins, cathe- thirds of the root. Sharpey’s fibres are inserted in
licidin LL-37, interleukin (IL)-8, IL-1α, IL-1β, this portion of cementum, of which the overall
tumour necrosis factor-α, intercellular adhesion degree of mineralisation is 45–60%.
molecule-1 (ICAM-1), and lymphocyte function Cellular intrinsic fibre cementum also called
antigen-3 (LFA-3). as the secondary cementum or cellular cemen-
tum is present along the apical third or half of
1.1.2.1 Connective Tissue the root and in furcation areas. It is produced as a
The connective tissue below the junctional epi- repair tissue filling the resorptive defects and root
thelium differs structurally from that below the fractures. Cementoblasts produce intrinsic col-
gingival epithelium. Even when the periodontal lagen fibres and those cementoblasts entrapped
tissues are clinically healthy, there is always an in lacunae are called cementocytes. This type of
infiltrate of inflammatory cells, mainly com- cementum is less mineralised than the acellular
prising PNLs. Also, T-lymphocytes continually extrinsic fibre cementum.
The cementum at and immediately subjacent Enzymes like alkaline phosphatase, matrix
to the CEJ is of particular clinical importance in metalloproteinases, growth factors like TGF-β,
root planing procedures. Moreover, this junction IGF, and platelet-derived growth factor (PDGF),
is the reference point for major clinical periodon- and proteoglycans also seem to have regulatory
tal measurements. However, it does not exist in functions on cementoblast differentiation and
all teeth; in about 5–10% of cases cementum and activity.
enamel fails to meet leaving dentine exposed to
the oral cavity.
In normal and healthy periodontium, cemen- 1.1.4 Periodontal Ligament
tum is placed in subgingival position and can
become exposed to the oral cavity when there Periodontal ligament is the soft, specialised con-
is gingival recession. In this case, organic sub- nective tissue between the root cementum and
stances, inorganic ions, and even bacteria can alveolar bone. It communicates with the marrow
penetrate cementum. Indeed, bacterial penetra- spaces through vascular channels in the bone. Its
tion to cementum is common in periodontitis width varies between 0.15 and 0.38 mm and its
and non-surgical periodontal treatment aims to thinnest part is located around the middle third
remove this infected cementum layer from the of the root length. Its thickness progressively
root surface. decreases with age. Due to its resilience, peri-
Overall cementum contains about 50% min- odontal ligament has unique functions such as
eral and 50% organic matrix. Its mineral content acting as a shock absorber against the physiolog-
is about 65% by weight, which is a little more ical and even traumatic forces coming towards
than that of bone. Approximately, 50% of the the teeth. Moreover, it has sensory receptors
inorganic component of cementum is hydroxy- necessary for the proper positioning of the jaws
apatite and 90% of the organic component is during mastication. It is also unique with its
type I and III collagens (Birkedal-Hansen et al. cell reservoir for tissue homeostasis and repair/
1977). Type III and type XII collagens are also regeneration.
found in high concentrations. There are trace Fibroblasts are the principal cells of the peri-
amounts of other collagens, including type V, VI, odontal ligament and they are characterised by
and XIV. Moreover, there are non-collagenous rapid turnover of the collagen content in the
matrix proteins, which are also found in alveolar extracellular matrix. There are also epithelial
bone (Bosshardt 2005). Among these there are cells in the periodontal ligament that are rem-
bone sialoprotein, dentin sialoprotein, fibronec- nants of Malassez. Their function is unclear but it
tin, osteocalcin, osteonectin, osteopontin, tenas- has been suggested that they may be involved in
cin, proteoglycans, proteolipids, and numerous periodontal repair/regeneration. Moreover, there
growth factors such as insulin-like growth factor are undifferentiated mesenchymal cells in the
(IGF). Osteocalcin is a marker for maturation of periodontal ligament. During periodontal wound
osteoblasts, odontoblasts, and cementoblasts. healing, the periodontal ligament cells contrib-
ute not only for its own repair but also for that
1.1.3.1 M olecular Factors that Regulate of alveolar bone and cementum (Beertsen et al.
Cementogenesis 1997; Karring et al. 1993).
Bone morphogenetic proteins (BMP): These pro- Collagen is a protein composed of different
teins are the members of the transforming growth amino acids, the most important of which are gly-
factor-β (TGF-β) superfamily. Their exact func- cine, proline, hydroxyproline, and hydroxylysine
tions have not been clarified but it is known that (Carneireo and Fava de Moraes 1965). Collagen is
BMP-2, -4, and -7 promote the differentiation of synthesised by fibroblasts, chondroblasts, osteo-
preosteoblasts and putative cementoblast precur- blasts, odontoblasts, and other cells. The predom-
sor cells. inant collagens of the periodontal ligament are
1.1 Healthy Periodontal Tissues 5
type I, III, and XII. The collagen fibrils arranged Within the context of formative and remod-
in definite and distinct fibre bundles are termed elling function, the periodontal ligament cells
as principal fibres. The embedded portions of the participate in the formation and resorption of
collagen fibres are called Sharpey’s fibres. There cementum and bone and in the repair of injuries.
are also elastic fibres in the periodontal ligament Finally, within the context of nutritional and
and they are oxytalan in nature. These fibres run sensory functions, the periodontal ligament sup-
more or less vertically from the cementum sur- plies nutrients to the cementum, bone, and also
face and form a three dimensional network that gingiva by way of blood vessels and provides
surrounds the root and terminates in the apical lymphatic drainage. There are abundant sen-
complex of arteries, veins, and lymphatics. These sory nerve fibres capable of transmitting tactile,
elastic fibres can expand in response to tensional pressure, and pain sensations by the trigeminal
forces. There are also non- collagenous matrix pathways.
proteins in the periodontal ligament and these Periodontal ligament can adapt to functional
include alkaline phosphatase, proteoglycans, and changes. In case the functional demand increases,
glycoproteins such as tenascin and fibronectin. the width of periodontal ligament can increase
Tenascin is present in attachment zones along up to 50% and the fibre bundles also increase
cementum and bone (Lukinmaa et al. 1991). in thickness. On the opposite, if the functional
Fibronectin and vitronectin are found in collagen demand decreases, the ligament becomes nar-
fibrils. rower and the number as well as the thickness of
Cellular component of periodontal ligament the fibre bundles also decreases.
is mainly formed by connective tissue cells,
epithelial rest cells, immune system cells, and
cells associated with neurovascular elements 1.1.5 Alveolar Bone
(Berkovitz and Shore 1982).
Periodontal ligament also has a ground sub- The alveolar bone is the portion of the jaws that
stance filling the spaces between the cells and contain the roots of the teeth. It forms when the
the fibres. The major components of this ground tooth erupts to provide the osseous attachment to
substance are glycosaminoglycans and glycopro- the forming periodontal ligament. Accordingly,
teins. Main glycosaminoglycans are hyaluronic it disappears gradually when the tooth is lost.
acid and proteoglycans, whereas the main glyco- According to the stage of development and
proteins are fibronectin and laminin. The water microstructure, bone can be divided into differ-
content of periodontal ligament is high reaching ent types such as primary (woven), secondary
about 70%. (lamellar), cancellous (trabecular), and compact
The functions of periodontal ligament can (cortical) (Buck and Dumanian 2012). There are
be divided into three major groups; (1) physical outer cortical plates at both sides of the alveol
functions, (2) formative and remodelling func- and the spongious/trabecular bone between them.
tions, and (3) nutritional and sensory functions. The bone lining the socket is called as the bundle
Within the context of physical functions peri- bone since it is the region of attachment for the
odontal ligament provides a soft tissue barrier periodontal ligament fibre bundles. The corti-
for the vessels and nerves to protect them from cal plates consist of surface layers supported by
injury by mechanical forces. Periodontal liga- Haversian systems. The trabecular or spongious
ment transfers the occlusal forces to the alveolar bone also consists of bone disposed in lamellae,
bone, attaches the teeth to the bone, and provides with Haversian systems.
resistance towards the occlusal forces by shock The turnover of the alveolar bone is very rapid
absorption. Periodontal ligament also has a role and following tooth extraction the edentulous part
in the maintenance of the gingival tissues in their of the alveolar bone is resorbed in both horizontal
proper relationship to the teeth. and vertical directions. The factors that control
homeostasis of the periodontal tissues still need gingival plexus is located beneath the junctional
to be better explained. If and when these mecha- epithelium.
nisms are fully understood, it may be possible to
guide tissue healing after non-surgical or surgical
periodontal treatment. 1.3 Lymphatic System
With a macro-scale; collagen fibres are aligned of the Periodontium
according to the mechanical and functional
requirements of the tissue and with a nano-scale; The smallest lymph vessels, the lymph capillar-
cross-linked collagen matrices are embedded ies, form an extensive network in the connective
within a mineralised matrix (Bartold et al. 2019). tissue. The lymph is absorbed from the tissue
Similar to the other periodontal tissues, the pre- fluid through the thin walls into the lymph cap-
dominant organic component of the alveolar bone illaries. The lymph vessels are similar to veins
are type I and III collagens (Wang et al. 1980). as they are provided with valves. The periodon-
There are also biologically active polypeptides tal tissues have connections with the submental,
such as bone sialoprotein and osteopontin (Chen deep cervical, submandibular, and jugulodigas-
et al. 1993). The major proteoglycans are rich in tric lymph nodes.
chondroitin sulphate (Bartold 1990; Waddington
and Embery 1991).
The cellular component of alveolar bone 1.4 Nerves of the Periodontium
includes osteoblasts that differentiate from plu-
ripotent follicle cells. Then, there are osteocytes The periodontium contains mechanoreceptors
that are enclosed within spaces called lacunae. that record pain, touch, and pressure. In addition
Osteoclasts are bone-resorbing cells that origi- to these, the periodontal ligament also contains
nate from haematopoietic tissue. Active osteo- proprioreceptors that give information about the
clasts possess an elaborately developed ruffled movements and positions. The small nerves of
border from which the hydrolytic enzymes are the periodontium follow almost the same course
released (Vaes 1988). with the blood vessels. Gingival innervation is
Alveolar bone has a number of functions; it derived from fibres arising from nerves in the
provides mechanical support and protection, periodontal ligament as well as from the labial,
maintains the mineral homeostasis, haematopoi- buccal, and palatal nerves.
esis, and also has endocrine functions (Florencio-
Silva et al. 2015).
1.5 Stem Cells
of the Periodontium
1.2 Blood Supply
of the Periodontium Stem cells in general originate from four sources:
embryonic tissues, foetal tissues, postnatal tis-
The gingiva, periodontal ligament, and alveo- sues, and reprogrammed differentiated somatic
lar bone are rich in blood vessels, whereas the cells that are termed “inducible pluripotent stem
cementum is an avascular tissue. The gingiva cells” (Lin et al. 2008). Mesenchymal stem cells
receives its blood supply from the supraperi- (MSC) include cells derived from nearly all tis-
osteal blood vessels, vessels of the periodon- sues in the human body and depending on their
tal ligament, and also from the arterioles that source these cells can differentiate into adi-
emerge from the alveolar crest to the interdental pocytes, osteoblasts, chondrocytes, tenocytes,
septa. Subepithelial plexus is located immedi- skeletal myocytes, and visceral stromal cells
ately beneath the oral epithelium. The capillary (Gronthos et al. 2003; Horwitz et al. 1999; Jiang
loops reach into the oral epithelium. The dento- et al. 2002).
References 7
References Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW,

Gordon PL, Neel M, et al. Transplantability and thera-
peutic effects of bone marrow-derived mesenchymal
Bartold PM. A biochemical and immunohistochemical
cells in children with osteogenesis imperfect. Nature
study of the proteoglycans of alveolar bone. J Dent
Med. 1999;5:309–13.
Res. 1990;69:7–19.
Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE,
Bartold P, Gronthos S, Haynes D, Ivanovski S.
Keene CD, Ortiz-Gonzales XR, et al. Pluripotency of
Mesenchymal stem cells and biologic factors
mesenchymal stem cells derived from adult marrow.
leading to bone formation. J Clin Periodontol.
Nature. 2002;418:41–9.
2019;46(Suppl.21):12–32.
Karring T, Ostergaard E, Loe H. Conservation of tis-
Beertsen W, Van Den Bos T, Everst V. Continuous growth
sue specificity after heterotopic transplantation of
of acellular extrinsic fiber cementum: a review. Acta
gingiva and alveolar mucosa. J Periodontal Res.
Med Dent Helv. 1997;2:103–15.
1971;6:282–93.
Berkovitz BKB, Shore RC. Cells of the periodontal liga-
Karring T, Lang NP, Loe H. The role of gingival connec-
ment. In: Berkovitz BKB, Moxham BJ, Newman HE,
tive tissue in determining epithelial differentiation. J
editors. The periodontal ligament in health and dis-
Periodontal Res. 1975;10:1–11.
ease. London: Pergamon Press; 1982.
Karring T, Nyman S, Gottlow J, Laurell L. Development
Birkedal-Hansen H, Butler WT, Taylor RE. Proteins of
of the biological concept of guided tissue regeneration-
the periodontium. Characterization of the insoluble
animal and human studies. Periodontol 2000.
collagens of bovine dental cementum. Calcif Tiss Res.
1993;1:26–35.
1977;23:39–44.
Lin NH, Gronthos S, Bartold PM. Stem cells and peri-
Bosshardt DD. Are cementoblasts a subpopulation of
odontal regeneration. Aust Dent J. 2008;53:108–21.
osteoblasts or a unique phenotype? J Dent Res.
Lukinmaa PL, Mackie EJ, Thesleff
2005;84:390–406.
I. Immunohistochemical localization of the matrix
Buck DW, Dumanian GA. Bone biology and physiol-
glycoproteins-tenascin and the ED-sequence-
ogy: part I. the fundamentals. Plastic Reconst Surg.
containing form of cellular fibronectin in human per-
2012;129:1314–20.
manent teeth and periodontal ligament. J Dent Res.
Carneiro J, Fava de Moraes F. Radioautographic
1991;70:19–26.
visualisation of collagen metabolism in the peri-
Narayanan AS, Clagett JA, Page RC. Effect of inflamma-
odontal tissues of the mouse. Arch Oral Biol.
tion on the distribution of collagen types I, III, IV, and
1965;10:833–46.
V and type I trimer and fibronection in human gingi-
Chavrier C, Couble ML, Magloire H, Grimaud JA.
vae. J Dent Res. 1985;64:1111–6.
Connective tissue organisation of healthy human gin-
Romanos G, Schröter-Kermani C, Hinz N, Bernimoulin
giva. Ultrastructural localization of collagen types
J-P. Immunohistochemical distribution of the colla-
I-III-IV. J Periodontal Res. 1984;19:221–9.
gen types IV, V, VI, and glycoprotein laminin in the
Chen J, McCulloch CA, Sodek J. Bone sialoprotein in
healthy rat, marmoset (Callithrix jacchus) and human
developing porcine dental tissues: cellular expression
gingivae. Matrix. 1991;11:125–32.
and comparison of tissue localization with osteopontin
Schroeder HE. Biological structure of the normal and dis-
and osteonectin. Arch Oral Biol. 1993;38:241–9.
eased periodontium-preface. Periodontol. 1997;13:17.
Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simoes MJ,
Selvig KA. The fine structure of human cementum. Acta
Cerri PS. Biology of bone tissue: structure, function,
Odontol Scand. 1965;23:423–41.
and factors that influence bone cells. Biomed Res Int.
Vaes G. Cellular biology and biochemical mechanism of
2015;2015:421746.
bone resorption. Clin Orthop. 1988;231:239–71.
Frank DE, Carter WG. Laminin 5 deposition regulates
Waddington RJ, Embery G. Structural characterization of
keratinocyte polarisation and persistent migration. J
human alveolar bone proteoglycans. Arch Oral Biol.
Cell Sci. 2004;117:1351–63.
1991;36:859–66.
Gronthos S, Chen S, Wang CY, Robey PG, Shi S.
Wang HM, Nanda V, Rao LG, Melcher AH, Heersche
Telomerase accelerates of osteoclastogenesis of
JN, Sodek J. Specific immunohistochemical localiza-
bone marrow stromal stem cells by upregulation of
tion of type III collagen in porcine periodontal tis-
CBFA1, osterix, and osteoclacin. J Bone Miner Res.
sues using the peroxidase-antiperoxidase method. J
2003;18:716–22.
Histochem Cytochem. 1980;28:1215–23.
Nature of Periodontal Diseases
2
The clinical manifestations of periodontal dis- Two critical factors are now regarded as deter-
ease are the result of very complex interactions mining whether bone loss will occur and these
between the microorganisms in the oral cavity are; the concentration of inflammatory media-
that form the microbial dental plaque and the tors present in gingival tissue to be sufficient to
host response towards the microorganisms and activate pathways leading to bone resorption and
their virulence factors. It is clear that periodon- the other is the penetration of the inflammatory
tal diseases are multifactorial and apart from the mediators to gingival tissue to reach a critical
microbial factors that trigger the host immune distance to alveolar bone (Graves and Cochran
response, the genetic background of the host, the 2003). Hence, bacteria are necessary for disease
systemic health, environmental conditions like initiation, but they are not sufficient to cause tis-
smoking and psychological stress, and various sue destruction (Page 1998). It is becoming quite
medications used for the treatment of systemic clear that the mechanisms for soft tissue destruc-
diseases can all affect the clinical outcome. tion are not completely same with those for cal-
cified tissue destruction. There is a continuous
remodelling in soft and hard tissues of periodon-
2.1 Inflammation tium, but the mechanisms of tissue renewal in
health differ from the pathogenic mechanism act-
Inflammation is the central pathologic feature ing in disease. Possibly, not only the main actors,
of periodontal disease and the microbial den- but also the reactions or interactions may differ
tal plaque is the major aetiological factor. The in this context.
immune and inflammatory responses are critical Periodontitis is described as a multifacto-
to the pathogenesis of periodontitis. The initial rial, irreversible, and cumulative condition,
response to the oral biofilm is a local inflamma- initiated and propagated by bacteria and host
tory reaction that activates the innate immune factors (Kinane 2001). It continues to be the
system (Graves and Cochran 2003; Garlet et al. most common cause of tooth loss worldwide.
2006). In case, this innate inflammatory response The immune and inflammatory responses are
is not controlled by feedback mechanisms or the orchestrated by a number of host-related fac-
host cells are hyper reactive, an array of vari- tors, either intrinsic or acquired (Taubman et al.
ous cytokines, enzymes, and other mediators are 2005). Under normal physiological conditions
released leading to connective tissue destruction there is a balance between bone formation and
and bone resorption. In case of periodontitis, bone resorption. In other words, osteoblastic
there are also alterations in bone metabolism. and osteoclastic functions are balanced. Bone
© Springer Nature Switzerland AG 2020 9

N. Buduneli, Biomarkers in Periodontal Health and Disease,
https://doi.org/10.1007/978-3-030-37317-7_2
10 2 Nature of Periodontal Diseases
homeostasis is maintained as long as this balance 2000; Rubin and Greenfield 2005). Both experi-
is preserved. When the structural integrity and/ mental studies in animal models and human
or calcium metabolism is altered, this balance is studies indicated that multinucleated osteoclasts
lost towards either increased bone formation or resorb alveolar bone. A variety of cytokines play
bone resorption. There are examples of systemic role in formation of cytokines (Fig. 2.1). The
diseases/conditions such as rheumatoid arthritis relationship between the immune system and
and osteoporosis and also local diseases such as bone metabolism has been termed “osteoimmu-
periodontitis. nology” and this is a rapidly progressing field
A principal feature of inflammatory peri- of research (Arron and Choi 2000). Clarifying
odontitis is enhanced osteoclast activity with- the mechanism of osteoimmunology seems to
out a corresponding increase in bone formation. be promising for the development of new pre-
Osteoclasts are the principal cells responsible vention and treatment modalities for bone loss
for bone resorption in periodontitis that are mul- in periodontitis. As clearly explained recently
tinucleated cells deriving from the monocyte- by Bosshardt (2018) transformation of the junc-
macrophage lineage (Boyle et al. 2003; Lerner tional epithelium to the pocket epithelium is
Fig. 2.1 Inflammatory

mechanisms in alveolar
bone resorption
LPS
Bacterial antigens
Microbial Challenge
Epithelial Cells
Fibroblasts Endothelial Cells
Inflammatory
Mediators
Immune Cells
MMPs
Connective Tissue
Destruction
Bone Resorption
PGE2
Fibroblasts
2.2 Pathogen Microorganisms 11
critical in the onset of periodontitis. The time- vitis to periodontitis. There is irreversible tissue
point of this transformation is regarded as piv- destruction with attachment loss, bone resorp-
otal for the pocket formation. Bosshardt (2018) tion, and connective tissue degradation. Bone
and Nibali (2018) suggested that the influence loss becomes clinically detectable. This model
of virulence factors might be important in the indicated that most of the tissue destruction in
breakdown of the junctional epithelium leading periodontitis is caused by host responses to the
to pocket formation. The biofilm’s influences biofilm microorganisms.
on the junctional epithelium destabilising it by The old concept that untreated gingivitis
thinning and/or ulceration that results in fur- would inevitably progress to periodontitis has
ther subgingival spread of the bacteria are quite been refuted by the data from longitudinal epide-
clear. miologic studies (Ismail et al. 1990; Listgarten
A variety of molecular, cellular, and immuno- et al. 1985; Löe et al. 1978, 1986, 1992).
histochemical events take place during the pro- Gingivitis always precedes periodontitis but not
gression of gingivitis to periodontitis (Kurgan all cases of gingivitis progresses to periodonti-
and Kantarci 2018). Histologically, there are four tis. On the contrary, only a fraction of untreated
phases in this progression; initial lesion, early sites with gingivitis progressed to periodonti-
lesion, established lesion, and advanced lesion tis during the observation period. Later studies
(Page and Schroeder 1976). The initial lesion is revealed that untreated periodontitis often pro-
the response of resident leukocytes and endothe- gresses in people who are not on regular main-
lial cells to the dental biofilm. tenance recall programs (Axelsson and Lindhe
At this stage, there is no clinical sign of inflam- 1978, 1981). It then became clear that there was
mation and this lesion can only be detected by no way to determine either the risk or the pres-
histological investigation. Upon stimulus from ence of periodontal disease activity at a single
bacteria and their virulence factors, junctional visit (Hancock 1981).
epithelium cells produce cytokines, neutrons pro- Today, it is accepted that anything that
duce neuropeptides, vascular changes comprising increases susceptibility to infections, or alters
vasodilatation and increase in permeability occur. their destructive course, may serve as a risk factor
Neutrophils leave the vessels and start migrating for periodontitis. Risk factors may be modifiable
towards the centre of inflammation. In the early or nonmodifiable. However, currently, there is no
lesion, the number of neutrophils is increased in fully validated formal risk-assessment method
the inflamed connective tissue and macrophages, for estimating the risk of progression, or the
lymphocytes, plasma cells, and mast cells start to recurrence of periodontitis (Garcia et al. 2009;
appear in the lesion. The junctional epithelium Loos et al. 2005).
proliferates forming rete pegs. Early clinical
signs of inflammation such as redness and bleed-
ing become visible. Flow of the gingival cre- 2.2 Pathogen Microorganisms
vicular fluid increases. The established lesion is
considered as the stage of transition from innate Since the first reports showing the role of bacteria
response to acquired immune response, where in periodontal disease onset, there have been sig-
there are dominating numbers of T-lymphocytes, nificant changes in the context of microbiological
macrophages, B-lymphocytes, and plasma cells. aetiology of periodontal diseases (Guerini 1909,
There is an increase in blood flow and colla- 1981). First, there was the “non-specific plaque
genolytic activity. Collagen production by fibro- hypothesis” stating that the extent and severity of
blasts is also increased. Clinically, this stage is periodontal disease are proportional to the amount
recognised as moderate to severe gingivitis with of plaque accumulating on teeth surfaces. This
easily detectable changes in the colour, contour, hypothesis was refuted, as there were cases with
consistence changes in gingiva. The final stage of significant amounts of plaque but no clear sign or
advanced lesion defines the transition from gingi- symptom of periodontal disease. Then came the
“specific plaque hypothesis” claiming that some The exact mechanisms of periodontal tissue
certain bacteria rather than the bulk of plaque play breakdown are not clearly understood but disease
a major role in the onset and progression of peri- onset and progression invariably involves a dis-
odontal disease Löesche (Löesche 1976). So, the ruption of the homeostasis or balance between
content of plaque became much more important the resident microbiota and the host (Listgarten
than its amount. Later on, research revealed that 1986; Darveau 2010). Periodontal homeostasis
more or less same bacteria species were present can be disrupted by a variety of host- or microbe-
in the healthy and diseased individuals as well as related factors. Congenital or acquired host
the healthy and diseased sites. Hence, the specific immunodeficiencies, immunoregulatory defects
plaque hypothesis was also refuted. The third associated with mutations or polymorphisms, old
plaque hypothesis; “ecological plaque hypoth- age, systemic diseases such as diabetes, obesity,
esis” included the environmental factors and the environmental factors (smoking, diet, and stress),
host into the frame together with the bacteria epigenetic modifications in response to environ-
in the plaque; the start and progression of peri- mental changes, and the presence of keystone
odontal disease is dependent on the presence of pathogens can transform a symbiotic microbiota
pathogenic bacteria in a susceptible host and envi- into a dysbiotic one (Stabholz et al. 2010; Zhou
ronmental factors, such as smoking, uncontrolled et al. 2011; Eskan et al. 2012; Hajishengallis
diabetes, genetic background, etc., increase the et al. 2012; Laine et al. 2012; Divaris et al. 2013;
severity of periodontal tissue destruction (Marsh Lindroth and Park 2013; Hajishengallis 2014).
2003). Today, this multifactorial scenario contin- The dysbiosis is not dependent so much on the
ues to be the most appropriate to explain the patho- particular microbial roster but rather on the
genic mechanisms of periodontitis (Fig. 2.2). specific gene combinations or collective viru-
Fig. 2.2 Multifactorial Intrinsic

pathogenic mechanisms
acting in periodontitis
Systemic
(blood)
Genetics
Saliva
Gingival crevicular fluid

Epigenetics
Gingiva
Pathogenic
Bacteria
Immune
response
& cytokines Dysbiosis
Environmental
Factors
- Infection
- Nutrition
- Smoking
- Psychological Stress
Extrinsic
2.2 Pathogen Microorganisms 13
lence activity within the microbial community organism should possess an array of virulence
(Hajishengallis and Lamont 2012). Accordingly, factors that can be linked to the pathogenesis of
a recent study employed gene expression pro- periodontal inflammation. “Socransky Criteria”
filing to characterise patient-matched healthy were used to generate lists of periodontopatho-
and disease-associated periodontal microbiotas gens in the World Workshop held in 1996 (Genco
(Jorth et al. 2014). It was reported that disease- et al. 1996). The workshop participants agreed
associated microbial communities exhibit highly that there is a strong evidence for pathogen sta-
conserved metabolic gene expression profiles, tus of Porphyromonas gingivalis, Tannerella
despite high interpatient variability in microbial forsythia, and Aggregatibacter actinomycetem-
composition. comitans. Moderate evidence exists to support
Sigmund Socransky understood that peri- the pathogenic role of Campylobacter rectus,
odontal infections were caused by organised Eubacterium nodatum, Prevotella intermedia/
communities of bacteria in which some micro- nigrescens, Parvimonas micra, Treponema den-
organisms were more important than others from ticola, and the Streptococcus milleri. During the
an etiological point of view and he proposed a following years studies were published focus-
set of criteria to be used while determining if a ing on one or two of these putative pathogens.
microorganism is likely to be an etiological agent However, this attitude could never reflect the
in periodontal diseases (Socransky 1979). These truth, as it has never been accepted that periodon-
criteria were patterned after Koch’s postulates tal diseases occur as a monoinfection. Indeed,
and included the following: association with dis- the complex metabolic interactions between dif-
ease; elimination or suppression of the organism ferent species of bacteria have a greater role in
results in disease remission; host response (i.e., the tissue destruction rather than the virulence
detection of adaptive immune responses to the factors of one or two specific bacteria (Fig. 2.3).
organism); demonstration that the organism is Periodontal diseases are polymicrobial infec-
pathogenic in an experimental animal; and—the tions (Socransky and Haffajee 2005). Indeed, the
• Crevicular/Junctional Epithelium & • TIMPs

LPS, DNA other Periodontal Ligament Cells • MMPs
• Activation of NF-Kβ & AP-1 • Osteoclast activation/
• Receptor & non-receptor mediated
differentiation
TNF-a
Oxidative Tissue Damage

Stress
Inflammatory cytokines,
chemokines e.g.
TNF-α, IL-1, IL-8,
GM-CSF, E-selectin
Periodontal Pathogens
• TNF-a
• LPS Generation of ROS
by fibroblasts & Release of traditional inflammatory mediators.
PMNL Generation of oxidation products: Lipid
• IL-8 peroxides, Oxidized proteins.
Cell Wall • GM-CSF Inactivation of TIMPs.
Components • LPS
• TNF-a Recruitment &
activation of hyper-
responsive PMNL
Fig. 2.3 Complex interactions between pathogen microorganisms and host response in the aetiopathogenesis of
periodontitis
polymicrobial nature of periodontitis explains Oral epithelial cells have tight intercel-
why routine microbial testing, as part of the lular junctions that form a mechanical bar-
treatment planning for periodontitis appears to rier to the entry of bacteria and their toxins.
have limited clinical value (Shaddox and Walker Lipopolysaccharide (LPS) is the cell-wall com-
2009). Accordingly, a systematic review failed to ponent of gram-negative bacteria that triggers
report high-level evidence supporting the diag- host response. Dendritic cells present antigens
nostic value of microbial testing in the manage- such as LPS to other immune cells for antibody
ment of periodontitis (Listgarten and Loomer production. Recognition of innate immune sig-
2003). The microbial component of periodontal nals by dendritic cells relies on a limited number
diseases is usually composed of flora bacteria of pathogen-related receptors. Toll-like receptors
that are more or less present in many individuals (TLRs) are among these proteins that regulate
in the society and sites in a mouth. These bacte- apoptosis, inflammation, and immune responses
ria are a normal part of the health-associated oral (Anderson 2000). This family of receptors are
microbiota and only become pathogens when expressed on lymphocytes, osteoclast precursors,
there is a major disturbance in the host-microbe macrophages, osteoblasts, epithelial cells, and
homeostasis (Armitage 2013). Therefore, the stromal cells (Hayashi et al. 2003). Clinically
pathogens are considered as opportunistic and healthy gingival tissue also expresses a variety
endogenous. This issue decreases the utility of of TLRs possibly acting in the inflammatory
microbial testing for diagnostic and/or monitor- response of periodontium (Darveau 2010). Eleven
ing purposes. Such tests may be beneficial in different TLR molecules have been identified in
selected cases, where the response to periodontal human periodontal tissues so far (Liu et al. 2010).
treatment fails to be satisfactory or as expected. The binding of TLRs with pathogen-associated
molecules leads to the production of cytokines,
chemokines, and antimicrobial peptides. TLR-2
2.3 Immune Response and TLR-4 are the dominant ones in periodontal
tissues and they can differentiate microorganisms
Innate and adaptive host immune responses to from the host. TLRs are capable of recognising
the microorganisms in the oral biofilm lead to pathogens, can regulate a host innate immune
the destruction of periodontal tissues. The host response to periodontopathic bacteria and can
immune response can contribute to protective serve as a bridge between innate and adaptive
and/or destructive effects in periodontal diseases. immune responses (Song et al. 2017). They are
As part of the innate response, neutrophils pass likely to play a central role in the initiation and
from the highly vascularised gingival tissue to progression of periodontitis.
the gingival crevice and form a wall between the In healthy periodontium, there is a balance
host tissue and the dental plaque biofilm (Tonetti between pro- and anti-inflammatory cytokines
et al. 1998). Approximately, 30,000 polymorpho- and disruption of this balance in favour of pro-
nuclear neutrophils (PMNs) transit through peri- inflammatory cytokines may contribute to the
odontal tissue every minute. The architecture and periodontal tissue damage. Certain bacteria such
permeability of the junctional epithelium permit as P. gingivalis are suspected to have a role in the
this migration of cells. Adhesion molecules such disruption of this balance and tissue homeostasis.
as E-selectin, intercellular adhesion molecules However, no single oral bacteria species seems
(ICAMs), cytokines such as interleukin (IL)-8, to be the only disruptor. Rather than this, as bac-
and other molecules such as human β-defensins, terial numbers increase, the proteases found in
soluble and membrane-bound CD14, and the red complex bacteria (Porphyromonas gingi-
lipopolysaccharide-binding protein (LBP) all valis, Tannerella forsythia, and Aggregatibacter
affect immune cell functions against dental bio- actinomycetemcomitans) may further compro-
film bacteria (Tonetti et al. 1998; Jin and Darveau mise innate defence by inactivating potentially
2001; Jin et al. 2004; Ren et al. 2004). protective host responses (Darveau 2010).
2.5 Network of Cytokines and Chemokines 15
2.4 Osteoclastic Bone Proliferation and survival of preosteoclasts and

Resorption also mature osteoclasts are promoted by M-CSF
(Chambers 2000).
Enhanced osteoclast activity is a basic compo-
nent of bone loss in inflammatory periodontitis
(Cochran 2008, Gruber 2019). Particular attention 2.5 Network of Cytokines
focuses on receptor activator of NF-kappaB ligand and Chemokines
(RANKL), a member of the tumour necrosis fac-
tor ligand family, because this molecule plays a Cytokines and chemotactic cytokines (chemo-
key role in osteoclastogenesis (Yasuda et al. 1998; kines) transmit the messages between various
Kong et al. 1999). Osteoblasts are the major cells cells and the immune response is regulated by
expressing RANKL, but at sites of inflammation these interactions. Cytokines are low-molecular-
other cells such as fibroblasts, T-lymphocytes, weight proteins involved in the initiation as
B-lymphocytes also express this ligand (Teitelbaum well as progression of inflammation. Secretion
2007). Parathyroid hormone, vitamin D3, and cyto- of pro- inflammatory cytokines from a vari-
kines like interleukin (IL)-1, IL-11 also have regu- ety of cells usually starts with the activation
latory functions on RANKL expression (Lacey of nuclear factor kappaB (NFkB) (Hanada and
et al. 1998; Matsuzaki et al. 1998; Hofbauer and Yoshimura 2002) (Fig. 2.3). Resident cells like
Heufelder 2001; Caetoano- Lopes et al. 2009). epithelial cells, fibroblasts and blood cells like
Osteoprotegerin (OPG) is the natural inhibitor of neutrophils and macrophages secrete cytokines
RANK, it acts as a decoy, competes with RANK to during acute and early chronic phases of inflam-
bind RANKL. In case the concentration of OPG is mation, whereas lymphocytes secrete cyto-
high enough, it binds RANKL inhibiting the bind- kines during established and advanced phases
ing of RANK and RANKL. Human periodontal of inflammation. Interleukin (IL)-1 and IL-6
ligament cells, gingival fibroblasts, and epithelial are those cytokines first discovered within the
cells can produce OPG and inflammatory cyto- context of periodontal inflammation. They are
kines such as transforming growth factor-β (TGF- characteristically related with inflammatory cell
β) can modulate its expression (Sakata et al. 1999; migration and osteoclastogenesis (Fonseca et al.
Kanzaki et al. 2002). 2009). Tumour necrosis factor- alpha (TNF-α)
It was reported that the osteoblasts express is a multi-potent cytokine functioning from cell
more RANKL than do the osteoclasts (Fumoto migration to tissue destruction. TNF-α upregu-
et al. 2014). Hence, different than the previous lates secretion of IL-1beta and IL-6 and it is also
thoughts, osteoblasts are now considered to have correlated with extracellular matrix degradation
a significant role in osteoclastic bone resorp- and bone resorption via promoting MMPs and
tion. Osteoclasts can bind to mineralised bone RANKL (Fig. 2.4).
surface, but there is always a non-mineralised Pro-inflammatory cytokines such as IL-1β,
layer of bone called “osteoid” covering bone sur- IL-6, IL-11, IL-17, and TNF-α can induce
faces and the first step in bone resorption is the osteoclastogenesis by increasing the expression
degradation of this osteoid layer. Collagenolytic of RANKL and decreasing OPG production
enzymes of the flat and elongated cells at the top by osteoblasts/stromal cells (Nakashima et al.
of the osteoid degrade this non-mineralised layer 2000). When there is abundant OPG expression,
thereby enhancing osteoclastic bone resorption but reduced RANKL, the net ratio of RANKL/
(Chambers and Fuller 1985). OPG becomes smaller and the outcome is likely
Macrophage colony stimulating factor to be excessive formation of bone. On the con-
(M-CSF) produced mainly by osteoblasts or bone trary, when there is a relative decrease in OPG
marrow stromal cells plays a significant role in concentration, or an increase in that of RANKL,
osteoclast development and activation lead- or both happening at the same time, then there
ing to alveolar bone loss (Bartold et al. 2010). is an excessive bone resorption due to the net
INFLAMMATION
• IL-1 • IL-4 • IL-18

• IL-10 • IFN-β
• IL-6 • IL-12 • IFN-γ
• IL-11 • IL-13
• IL-17
• TNF-α Osteoblast/ stromal cells
• LIF
• OSM
RANKL / OPG
• Bradykinin CHEMOKINES
Osteoclast
• Kallidin progenitor
• Thrombin
Fig. 2.4 Cytokines and chemokines in bone resorption
increase in the RANKL/OPG ratio. IL-17 is of Chemokines are small proteins that play sig-
particular importance due to its increasing effect nificant roles in chemotactic migration of cells
on RANKL expression and concomitantly decreas- to the site of infection. Endothelial cells, epi-
ing effect on OPG expression in osteoblastic cells thelial cells, stromal cells, as well as leukocytes
in vitro and in vivo, thereby enhancing osteoclast can secrete chemokines. They are grouped as
formation and bone erosion in a mouse model homeostatic or inflammatory (Moser et al. 2004).
of arthritis (Lubberts et al. 2003). Just the oppo- They are essential signals for the trafficking of
site, anti-inflammatory cytokines such as IL-13 osteoblast and osteoclast precursors, potentially
and interferon (IFN)-γ, have lowering effect on modulating also bone homeostasis. Chemokines
RANKL expression and/or increasing effect on can effectively contribute to bone remodelling by
that of OPG, eventually inhibiting osteoclastogen- driving osteoblast migration and activation.
esis (Nakashima et al. 2000). IFN-γ also plays a
major role in B-cell maturation. It is present at high
levels in periodontal lesions and associated with 2.6 Lipid Mediators
progression of periodontitis (Dutzan et al. 2009). of Inflammation
IL-4 is another important anti-inflammatory
cytokine acting in proliferation of T-cells and Prostaglandins (PGs) are derived from the
regulating B-cell secretions. It inhibits the pro- hydrolysis of cell membrane phospholipids.
duction of MMPs and RANKL, at the same Arachidonic acid is metabolised by either lipoxy-
time induces upregulation of tissue inhibitors genases or cyclooxygenases (COXs). PGE2 is a
of MMPs (TIMPs) and OPG. It is regarded as a potent stimulator of alveolar bone resorption. At
protective cytokine in the pathogenesis of peri- high concentrations, PGE2 decreases the levels
odontal diseases. It also induces the production of IgG, but at low concentrations it has the poten-
of another anti-inflammatory cytokine IL-10. tial to increase IgG (Fig. 2.5).
This cytokine plays a direct protective role in tis- Offenbacher et al. (2007) proposed a “bio-
sue destruction by downregulating both MMPs logic systems model” as a critical framework
and RANKL. Transforming growth factor-beta with which the components of the periodontal
(TGF-β) regulates cell growth, differentiation, disease may be seen. This model incorporates all
and matrix production and also is a potent immu- components that contribute to the final clinical
nosuppressive factor that downregulates the tran- phenotype, which is the clinical presentation of
scription of pro-inflammatory cytokines such as the disease. Later on, the authors hypothesised
IL-1β and TNF-α. In active periodontal lesions, that there are different biologic factors underly-
the levels of TGF-β negatively correlate with ing periodontal disease in different individuals
those of RANKL (Dutzan et al. 2009). (Offenbacher et al. 2008).
References 17
Role of Lipid Mediators in Inflammation
COX 1 & 2
Prostaglandins • Pro-inflammatory
• Anti-inflammatory
Membrane 5-Lipoxygenase
Arachidonic Acid Leukotrienes • Pro-inflammatory
Phospholipids
Cell-Cell
Interactions
Lipoxins • Anti-inflammatory
Fig. 2.5 Lipid mediators acting in bone resorption
In the healthy state, there is a balance between notype seems to be the ultimate outcome of the
bone resorption and bone formation (Boyle et al. complex interactions between the biologic phe-
2003). Excessive bone formation can be observed notype in terms of cellular and molecular host
in certain inflammatory conditions such osteo- responses and surrogate biomarkers, genetic and
petrosis and excessive bone resorption can be epigenetic composition including race, age, and
observed in chronic diseases such as osteoporo- gender, and finally individual risk factors such
sis and periodontitis (Lerner 2006; Saidenberg- as smoking, diabetes, obesity, and the individual
Kermanach et al. 2004). Very recently, Lerner composition of the dental biofilm. The genotype
et al. (2019) outlined the complex events taking is a determining factor for predisposition as well
place in the osteoclastic bone resorption. First, as for the phenotype. Understanding the biologi-
secreted osteoclast factors such as bone mor- cal background of the phenotypes of periodontal
phogenetic protein (BMP)-6 act on osteoblasts. diseases may eventually help to establish prog-
Secondly, membrane-bound osteoclast-derived nosis and develop individually tailored treatment
factors act on osteoblasts. Thirdly, matrix-derived modalities for active and maintenance phases of
factors such as BMP-2,-4,-5,-6,-7,-9, insulin- periodontal therapy.
like growth factor (IGF)-1 act on osteoblasts.
Fourthly, factors such as TGF-β act directly on
osteoclasts. Then, there are factors such as IGF-1
References
acting indirectly on osteoclasts by regulating
RANKL/OPG ratio. Later on, osteocyte-derived Anderson KV. Toll signalling pathways in the innate
factors act on osteoblasts, and finally, osteocyte- immune response. Curr Opin Immunol. 2000;12:13–9.
derived factors act on osteoclasts. This scenario Armitage GC. Learned and unlearned concepts in peri-
odontal diagnostics: a 50-year perspective. Periodontol
clearly indicates that osteoclastic bone resorption 2000. 2013;62:20–36.
comprises very complex mechanisms and not Arron JR, Choi Y. Bone versus immune system. Nature.
only osteoclasts but also osteoblasts play critical 2000;408:535–6.
roles in osteoclastic bone resorption. Axelsson P, Lindhe J. Effect of controlled oral hygiene
procedures on caries and periodontal disease in adults.
J Clin Periodontol. 1978;5:133–51.
Axelsson P, Lindhe J. Effect of controlled oral hygiene
2.7 Conclusion procedures on caries and periodontal disease in
adults. Results after 6 years. J Clin Periodontol.
1981;8:239–48.
As a conclusion, the pathogenic mechanism act- Bartold PM, Cantley MD, Haynes DR. Mechanisms
ing in periodontal tissue destruction is clearly and control of pathologic bone loss in periodontitis.
complex and multifactorial. The clinical phe- Periodontol. 2010;53:55–69.
Bosshardt DD. The periodontal pocket: pathogenesis, Hajishengallis G, Darveau RP, Curtis MA. The
histopathology and consequences. Periodontol 2000. keystone- pathogen hypothesis. Nat Rev Microbiol.
2018;76:43–50. 2012;10:717–25.
Boyle WJ, Simonet WS, Lacey DL. Osteoclast differen- Hanada T, Yoshimura A. Regulation of cytokine signal-
tiation and activation. Nature. 2003;423:337–42. ling and inflammation. Cytokine Growth Factor Rev.
Caetoano-Lopes J, Canhao H, Fonseca JE. 2002;13:413–21.
Osteoimmunology—the hidden immune regulation of Hancock EB. Determination of periodontal disease activ-
bone. Autoimmun Rev. 2009;8:250–5. ity. J Periodontol. 1981;52:492–9.
Chambers TJ. Regulation of the differentiation and func- Hayashi S, Yamada T, Tsuneto M, Yamane T, Takahashi
tion of osteoclasts. J Pathol. 2000;192:4–13. M, Shultz LD, Yamazaki H. Distinct osteoclast pre-
Chambers TJ, Fuller K. Bone cells predispose bone sur- cursors in the bone marrow and extramedullary organs
faces to resorption by exposure of mineral to osteo- characterised by responsiveness to toll-like receptor
clastic contact. J Cell Sci. 1985;76:155–65. ligands and TNF-alpha. J Immunol. 2003;171:5130–9.
Cochran DL. Inflammation and bone loss in periodontal Hofbauer LC, Heufelder AE. Role of receptor activator
disease. J Periodontol. 2008;79:1569–76. of nuclear factor-kappaB ligand and osteoprotegerin in
Darveau RP. Periodontitis: a polymicrobial disruption of bone cell biology. J Mol Med. 2001;79:243–53.
host homeostasis. Nat Rev Microbiol. 2010;8:481–90. Ismail AI, Morrison EC, Burt BA, Caffesse RG, Kavanagh
Divaris K, Monda KL, North KE, et al. Exploring the MT. Natural history of periodontal disease in adults:
genetic basis of chronic periodontitis: a genome-wide findings from the Tecumseh periodontal disease study
association study. Hum Mol Genet. 2013;22:2312–24. 1959-87. J Dent Res. 1990;69:430–5.
Dutzan N, Vernal R, Hernandez M, Dezerega A, Rivera Jin L, Darveau RP. Soluble CD14 levels in gingival cre-
O, Silva N, Aguillon JC, Puente J, Pozo P, Gamonal vicular fluid of subjects with untreated adult periodon-
J. Levels of interferon-gamma and transcription factor titis. J Periodontol. 2001;72:634–40.
T-bet in progressive periodontal lesions in patients with Jin L, Ren L, Leung WK, Darveau RP. The in vivo expres-
chronic periodontitis. J Periodontol. 2009;80:290–6. sion of membrane-bound CD14 in periodontal health
Eskan MA, Jotwani R, Abe T, et al. The leukocyte integrin and disease. J Periodontol. 2004;75:578–85.
antagonist Del-1 inhibits IL-17-mediated inflamma- Jorth P, Turner KH, Gumus P, Nizam N, Buduneli N,
tory bone loss. Nat Immunol. 2012;13:465–73. Whiteley M. Metatranscriptomics of the human
Fonseca JE, Santos MJ, Canhao H, Choy E. Interleukin-6 oral microbiome during health and disease. MBio.
as a key player in systemic inflammation and joint 2014;5:e01012–4.
destruction. Autoimmun Rev. 2009;8:538–42. Kanzaki H, Chiba M, Shimizu Y, Mitanı H. Periodontal
Fumoto T, Takeshita S, Ito M, Ikeda K. Physiological func- ligament cells under mechanical stress induce osteo-
tions of osteoblast lineage and T cell-derived RANKL in clastogenesis by receptor activator of nuclear factor
bone homeostasis. J Bone Miner Res. 2014;29:830–42. kappaB ligand up-regulation via prostaglandin E2
Garcia RI, Nunn ME, Dietrich T. Risk calculation and synthesis. J Bone Miner Res. 2002;17:210–20.
periodontal outcomes. Periodontol. 2009;50:65–77. Kinane DF. Causation and pathogenesis of periodontal
Garlet GP, Cardoso CR, Silva TA, et al. Cytokine pattern disease. Periodontol 2000. 2001;25:8–20.
determines the progression of experimental periodon- Kong YY, Feige U, Sarosi I, et al. Activated T cells
tal disease induced by Actinobacillus actinomycetem- regulate bone loss and joint destruction in adjuvant
comitans through the modulation of MMPs, RANKL, arthritis through osteoprotegerin ligand. Nature.
and their physiological inhibitors. Oral Microbiol 1999;402:304–9.
Immunol. 2006;21:12–20. Kurgan S, Kantarci A. Molecular basis for immunohisto-
Genco R, Kornman K, Williams R, et al. Consensus chemical and inflammatory changes during progres-
report. Periodontal disease: pathogenesis and micro- sion of gingivitis to periodontitis. Periodontol 2000.
bial factors. Ann Periodontol. 1996;1:926–32. 2018;76:51–67.
Graves DT, Cochran D. The contribution of interleukin- Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR,
1 and tumour necrosis factor to periodontal tissue
Burgess T, et al. Osteoprotegerin ligand is a cytokine
destruction. J Periodontol. 2003;74:391–401. that regulates osteoclast differentiation and activation.
Gruber R. Osteoimmunology: inflammatory osteoly- Cell. 1998;93:165–76.
sis and regeneration of the alveolar bone. J Clin Laine ML, Crielaard W, Loos BG. Genetic susceptibility
Periodontol. 2019;46(Suppl. 21):52–69. to periodontitis. Periodontol 2000. 2012;58:37–68.
Guerini V. History of dentistry. Philadelphia: Lea & Lerner UH. Osteoclast formation and resorption. Matrix
Febiger; 1909. Biol. 2000;19:107–20.
Guerini V. History of dentistry. Odontostomatol Proodos. Lerner UH. Inflammation-induced bone remodelling in peri-
1981;35:198–204. odontal disease and the influence of post-menopausal
Hajishengallis G. Aging and its impact on innate immu- osteoporosis. J Dent Res. 2006;85:596–607.
nity and inflammation: implications for periodontitis. Lerner UH, Kindstedt E, Lundberg P. The critical inter-
J Oral Biosci. 2014;56:30–7. play between bone resorbing and bone forming cells. J
Hajishengallis G, Lamont RJ. Beyond the red complex Clin Periodontol. 2019;21:33–51.
and into more complexity: the polymicrobial synergy Lindroth AM, Park YJ. Epigenetic biomarkers: a step for-
and dysbiosis (PSD) model of periodontal disease eti- ward for understanding periodontitis. J Periodontal
ology. Mol Oral Microbiol. 2012;27:409–19. Implant Sci. 2013;43:111–20.
References 19
Listgarten MA. Pathogenesis of periodontitis. J Clin Offenbacher S, Barros SP, Beck JD. Rethinking periodon-
Periodontol. 1986;13:418–25. tal inflammation. J Periodontol. 2008;79:1577–84.
Listgarten MA, Loomer PM. Microbial identification in Page RC. The pathobiology of periodontal diseases may
the management of periodontal diseases. A systematic affect systemic diseases: inversion of a paradigm. Ann
review. Ann Periodontol. 2003;8:182–92. Periodontol. 1998;3:108–20.
Listgarten MA, Schiffer CC, Laster I. 3-year longi- Page RC, Schroeder HE. Pathogenesis of inflammatory
tudinal study of the periodontal status of an adult periodontal disease. A summary of current work. Lab
population with gingivitis. J Clin Periodontol. Invest. 1976;34:235–49.
1985;12:225–38. Ren L, Jin L, Leung WK. Local expression of
Liu YC, Lerner UH, Teng YT. Cytokine responses against lipopolysaccharide-binding protein in human gingival
periodontal infection: protective and destructive roles. tissues. J Periodontal Res. 2004;39:242–8.
Periodontol 2000. 2010;52:163–206. Rubin J, Greenfield E. Osteoclast origin and differentia-
Löe H, Anerud A, Boysen H, Smith M. The natural history tion. In: Bronner F, Frach-Carson MC, Rubin J, edi-
of periodontal disease in man: the rate of periodon- tors. Topics in bone biology-bone Resorption, vol. 2.
tal destruction before 40 year of age. J Periodontol. London: Springer; 2005. p. 1–23.
1978;49:607–20. Saidenberg-Kermanach N, Cohen-Solal M, Bessis N,
Löe H, Anerud A, Boysen H, Morrison E. Natural his- De Vernejoul MC, Boisser MC. Role for osteoprote-
tory of periodontal disease in man: rapid, mod- gerin in rheumatoid inflammation. Joint Bone Spine.
erate and no loss of attachment in Sri Lankan 2004;71:9–13.
laborers 14 to 46 years of age. J Clin Periodontol. Sakata M, Shiba H, Komatsuzawa H, Fujita T, Ohta
1986;13:431–40. K, Sugai M, Suginaka H, Kurihara H. Expression
Löe H, Anerud A, Boysen H. The natural history of of osteoprotegerin (osteoclastogenesis inhibitory
periodontal disease in man: prevalence, sever- factor) in cultures of human dental mesenchy-
ity, and extent of gingival recession. J Periodontol. mal cells and epithelial cells. J Bone Miner Res.
1992;63:489–95. 1999;14:1486–92.
Löesche WJ. Chemotherapy of dental plaque infections. Shaddox LM, Walker C. Microbial testing in periodontics:
Oral Sci Rev. 1976;9:65–107. value, limitations and future directions. Periodontol
Loos BG, John RP, Laine ML. Identification of genetic 2000. 2009;50:25–38.
risk factors for periodontitis and possible mecha- Socransky SS. Criteria for the infectious agents in den-
nisms of action. J Clin Periodontol. 2005;32(Suppl. tal caries and periodontal disease. J Clin Periodontol.
6):159–1679. 1979;6(Extra issue):16–21.
Lubberts E, Bersselaar L, Oppers-Walgreen B, et al. Socransky SS, Haffajee AD. Periodontal microbial ecol-
IL-17 promotes bone erosion in murine collagen- ogy. Periodontol 2000. 2005;38:135–87.
induced arthritis through loss of the receptor activa- Song B, Zhang YL, Chen LJ, Zhou T, Huang WK, Zhou
tor of NF-kappa B ligand/osteoprotegerin balance. J X, Shao LQ. The role of toll-like receptors in peri-
Immunol. 2003;170:2655–62. odontitis. Oral Dis. 2017;23:168–80.
Marsh PD. Are dental diseases examples of ecological Stabholz A, Soskolne WA, Shapira L. Genetic and
catastrophes? Microbiology. 2003;149:279–94. environmental risk factors for chronic periodon-
Matsuzaki K, Udagawa N, Takahashi N, Yamaguchi titis and aggressive periodontitis. Periodontol.
K, Yasuda H, Shima N, et al. Osteoclast differen- 2010;53:138–53.
tiation factor (ODF) induces osteoclast-like cell Taubman MA, Valvende P, Han X, Kawai T. Immune
formation in human peripheral blood mononuclear response: the key to bone resorption in periodontal
cell cultures. Biochem Biophys Res Commun. disease. J Periodontol. 2005;76:2033–41.
1998;246:199–204. Teitelbaum SL. Osteoclasts: what do they do and how do
Moser B, Wolf M, Walz A, Loetscher P. Chemokines: they do it? Am J Pathol. 2007;170:427–35.
multiple levels of leukocyte migration control. Trends Tonetti MS, Imboden MA, Lang NP. Neutrophil migra-
Immunol. 2004;25:75–84. tion into the gingival sulcus is associated with tran-
Nakashima T, Kobayashi Y, Yamasaki S, et al. Protein sepithelial gradients of interleukin-8 and ICAM-1. J
expression and functional difference of membrane- Periodontol. 1998;69:1139–47.
bound and soluble receptor activator of NF-kappaB Yasuda H, Shima N, Nakagawa N, et al. Osteoclast dif-
ligand: modulation of the expression by osteo- ferentiation factor is a ligand for osteoprotegerin/
tropic factors and cytokines. Biochem Biophys Res osteoclastogenesis-inhibitory factor and is identi-
Commun. 2000;275:768–75. cal to TRANCE/RANKL. Proc Natl Acad Sci USA.
Nibali L. Development of the gingival sulcus at the time 1998;95:3597–602.
of tooth eruption and the influence of genetic factors. Zhou Q, Leeman SE, Amar A. Signalling mechanisms
Periodontol 2000. 2018;76:35–42. in the restoration of impaired immune function due
Offenbacher S, Barros SP, Singer RE, Moss K, Williams to diet-induced obesity. Proc Natl Acad Sci USA.
RC, Beck JD. Periodontal disease at the biofilm- 2011;108:2867–72.
gingival interface. J Periodontol. 2007;78:1911–25.
Another random document with
no related content on Scribd:
print, and yet we had to send to England for paper to do the
job. Also all the pronunciation marks for Webster’s dictionary
were to be put in, and we did not have the type or the
matrices. I had to have the letters cut on wood, and matrices
made; this was a world of trouble. Some of the letters were
cut over half-a-dozen times or more, and after all they were
far from perfect. I also had a set of shaped music types cut,
and this took a deal of time and pains to get them all properly
cut, as also to get the matrices made. I finally succeeded
quite well in both respects.... I also experimented not a little in
stereotyping, and succeeded in doing fair work. I trained one
boy who stereotyped Matthew before I left. In order to carry it
on effectually and rapidly I had a furnace and press made and
fitted up, which after sundry changes worked very well.... I
also had a new style of case for Chinese type made, which I
think will be an improvement on the old. I also had a complete
and thorough overhauling of the matrices, reassorted them
all, and had new cases made. This was a serious job, but it
will I am sure prove a very great help to the efficient working
of the establishment.
He consented to manage the press only until a competent man

could be secured to take it off his hands. When casting about for
such a person, his mind had been directed to his brother John,
nearly a year before he was himself forced into this position. John
had hoped to go to college, and to prepare for the ministry, and to go
out as a missionary, but, on account of certain tendencies developed
as to his health, he was compelled to abandon his purpose. As to his
mechanical gifts and his ability to turn them into use in a great
variety of ways, he resembled Calvin; and the latter was so confident
that John could soon fit himself to be a competent superintendent of
the press at Shanghai that he advised the Board of Missions to make
inquiry in regard to him. The result was that eventually he was
selected for the place, and he arrived in China early in August, 1871.
Before he could satisfactorily enter on his duties it was necessary for
him to acquire some knowledge of the language and to acquaint
himself with the business committed to his charge. This detained
Calvin until late in that year; and after a period of some three months
spent at Tengchow, he returned to Shanghai to assist John in moving
the press to new and much better premises that had been
purchased. The moving proper was a heavy job, requiring a week of
hard, dirty labor. The distance was about a mile, mostly by water, but
by land a hundred or more yards at either end. While thus engaged,
although he was no longer officially at the head of the business, he
took the main charge, so as to allow his brother to give his time
chiefly to the acquisition of the language and to other things that he
needed to learn.
The new place is the same now occupied by the press in Peking
Road. Under the superintendency of Rev. G. F. Fitch, it has become
the center not only of the Presbyterian missions, but of the general
missionary activity all over China. In writing to his brother as early as
November, 1869, he said of this plant: “It is a very important place,
and would give you an extensive field for doing good. The
establishment is not very large, it is true, as compared with similar
establishments in such cities as New York or Philadelphia; yet it is
the largest and best of the kind in China. It not only does all the
printing for all our missionaries, but a great deal of job work for
others; besides making and selling a large amount of type.” After he
had completed his term of the management, and while helping John
to get into the traces, he wrote to one of the secretaries of the Board:
I am not in favor of enlargement, but I would be very sorry

to see the present efficiency of the press curtailed. It is doing
a great and a good work not only for our missions, but for all
China. It has exerted a prodigious collateral influence both in
China and in Japan, affording facilities for the production of all
kinds of scientific books, dictionaries, and so forth. Aside from
any general interest in the missionary work, having at no
small sacrifice left my proper work and given more than a
year to the press, and also having a brother here in charge of
it, I feel a lively interest in its future.
The last record that has come down to us concerning his work
there is: “We have just sold to the Chinese government a large font
of Chinese type. They are going to use movable metal type. This is a
large step for them to take, and it will do good. China yields slowly,
but she is bound to yield to Christianity and Christian civilization.”
At no subsequent period of his life had he any part in the
management of a printing establishment, but indirectly he continued
to have much to do with the press. He was a member of a joint
committee of the Shantung and the Peking mission, in charge of
publications, and as such he had to acquaint himself with what was
needed, and with what was offered, so as to pass intelligent
judgment. Unofficially and as a friend whose aid was solicited, he
revised one or more of the books which his associates submitted to
him for criticism. At the General Conference of Missionaries, held at
Shanghai in 1877, a committee, of which he was a member, was
appointed to take steps to secure the preparation of a series of
schoolbooks for use in mission schools. Not long afterward he
published an elaborate paper on the subject, discussing in it the
character which such publications should have, and especially
calling attention to the need of peculiar care as to the Chinese words
which ought to be employed in the treatises on the sciences. That
committee diligently set itself to work, and initiated measures for a
rather comprehensive set of books by various missionaries to meet
the want recognized in this general field. He was himself called upon
to prepare several books, some of which he was willing to undertake;
others he put aside as not properly falling to him. In one or two
instances he claimed for himself precedence as to treatises
suggested for others to write. Some friction occurred, and when the
Conference met again in 1890 that committee was discharged, and
an Educational Association, composed of missionaries familiar with
the needs of schools, and confining its functions more exclusively to
the publication of books for teaching—largely under his leadership—
was formed. He was its first chairman. This change he had warmly
favored, and he was an active member of the Association. In it he
was chairman of a committee on scientific terms in Chinese, a
subject of great difficulty, and of prime importance in the preparation
of text-books. In the subsequent years he was so much occupied
with the revision of the Mandarin Bible, and with other duties, that he
could give to the technical terms only a secondary place in his
activities. Still, six years after he accepted this chairmanship he
says: “I have collected a large number of lists of subjects for terms in
chemistry, physics, mathematics, astronomy, geology, metallurgy,
photography, watch-making, machinery, printing, music, mental and
moral philosophy, political economy, theology, and so forth.”
Subsequently he continued this work.
The first literary production of his own pen in Chinese was a tract
on infant baptism; this was called forth by local conditions at
Tengchow. A small sheet tract, entitled “A Prayer in Mandarin,” also
followed early. As chairman of the committee appointed by the
Educational Association, he made a report on chemical terms, and
recommended a new and distinctively Chinese method for the
symbols in that science. This was printed.
In a preliminary report of the Shanghai press, made in September,
1871, he, in a list of books in course of preparation, mentions under
his own name as author the following: “1. Catechism on Genesis,
with answers to the more difficult questions,—finished, needing only
a slight revision. 2. An explanation of the moral law as contained in
the ten commandments,—half-finished. 3. Scripture Text-Book and
Treasury, being Scripture references by subjects, supplying in great
part the place of a concordance,—one-third finished.” All of these
had been under way for several years, but had been frequently
shunted off the track by other imperative work. Very soon after that
date the catechism was published. He had a good deal to do with
Julia’s “Music Book,” especially in coining appropriate terminology,
though he never claimed joint authorship in it. Along with Dr. Nevius,
he published a hymn book for use in Chinese services; and down to
the close of his life, especially on a Sabbath when he did not preach,
he now and then made an additional Chinese version of a hymn. In
fact, whenever he heard a new hymn that especially moved him he
wished to enrich the native collection by a translation of it into their
speech. One which the Chinese came greatly to like was his
rendering of the Huguenot song, “My Lord and I.” A subject that was
always dominant in his mind and heart was the call to the ministry,
and it was significant that one of the last things on which he worked
was a translation of the hymn which has the refrain, “Here am I, send
me.” It was not quite finished when his illness compelled him to lay
down his pen; but recently at a meeting of the Chinese student
volunteers, constituting a company rising well toward one hundred
and fifty, that hymn was printed on cards, and a copy was given to
each of these candidates for the ministry. In 1907 he had carried a
theological class through the Westminster Shorter Catechism, and
as an outcome his translation was published. This is the last
religious book he made in Chinese. During his long service as a
missionary he taught a number of theological classes in various
studies, and his lectures were regarded as very superior, but he
published none of them.
His schoolbooks all originated in the necessities of his own work
as a teacher. The first thus to force itself upon his attention was an
arithmetic. He was already at work on it in 1868, and it went to press
while his brother John was superintending the plant at Shanghai.
The preparation of such a book, to one unacquainted with the
conditions under which this one was made, may seem to have been
a rather easy undertaking, and to have required little more than a
sufficient mastery of the Chinese language and of English; yet there
were some perplexing questions that arose in connection with it. For
instance, the method of writing numbers horizontally was wholly
unknown to the Chinese. Should the new arithmetic use the western,
or should it retain the Chinese method? To retain the Chinese would
be to train the pupils in a usage that would be confusing in
subsequent reading of western mathematics; to abandon it would be
equally confusing in printing the text of the book, which, according to
Chinese usage, must be arranged perpendicularly. The difficulty was
gotten over by duplicating each pattern example, giving it once
horizontally and once perpendicularly. Pupils using the book were
permitted to take their choice in performing their work, but in the text
proper all numbers appeared vertically. Such lines as those dividing
the numerator and denominator of a fraction stood perpendicularly,
with the figures to the right and the left. Until he published his
arithmetic, the Chinese numerals had been employed; he introduced
the Arabic. At the dawn of the new era subsequent to the Boxer
outbreak, almost the first book in demand by Chinese teachers and
pupils outside the mission schools was a western arithmetic; and
among others put upon the market were many “pirated” editions of
Mateer’s book, printed on cheap paper and with wooden blocks. The
publishers had not yet learned the significance of “copyright.” The
circulation of the book, however brought about, had at least the
effect of immediately increasing the reputation of its author among
the scholarly classes outside the church. Of the editions issued by
the press at Shanghai tens of thousands of copies have been sold.
Dr. Fitch writes that “it is impossible to state the total number,” and
that “the book has gone into all parts of the empire.”
In October, 1884, he submitted to the schoolbook committee of the
Educational Association the manuscript of his geometry, and in doing
so he said of it:
It is the result of much pains and labor.... The book is

written in plain Wen-li, and much pains has been taken to
make it smooth in style and accurate in meaning. In the few
equations used I have introduced the mathematical signs
employed in the West, of which I have given a full explanation
in the beginning of the book.... Mathematical signs and
symbols are a species of universal language, used alike by all
civilized nations, and it is unwise to change them until it is
absolutely necessary. The young men who have given most
effective assistance in the preparation of this geometry are
decided in their opinion that we should not change or garble
the mathematical symbolism of the West, but give it to them in
its integrity. The only change made is in writing equations
perpendicularly instead of horizontally,—a change which is
necessitated by the form of Chinese writing.
The book was published the following year. To the same

committee he reports in March, 1882, that his algebra was then all in
manuscript, and only needing revision and some rearrangement
before printing. The geometry was followed by his algebra, first part.
These have had a large sale, though, because fewer studied this
branch, not the equal of the arithmetic.
On January 14, 1908, he sent to the manager of the press the
preface to the second volume of his algebra, which covers the same
ground as the “University” edition in the United States. Of this Dr.
Hayes says: “Over twenty years ago he began the preparation of
Part II of his algebra, and the draft then made was used in
manuscript for many years. Other duties pressed upon him, and he
was compelled to lay it away unfinished. Yet he had not forgotten it,
but from time to time he would make a step in advance. It was only a
few months before his death that the work was completed and
published.”
There were a number of other books which he planned, on some
of which he did considerable work, but none of which he completed.
One of these was so colossal in its projected scope and scholarship
that it deserves special notice because indicative of the large things
to which early in his missionary career he was already eager to give
his time and abilities. This was a Mandarin dictionary. In its
preparation he sought to associate with himself Rev. Chauncey
Goodrich, of Peking; and in writing to him under date of June 6,
1874, he thus stated his conception of the work:
My idea of the book is a dictionary of the spoken language

of north China, in all its length and breadth, including on the
one hand all the colloquialisms that the people use in
everyday life,—all they use in Chi-li and in Shantung, and in
all the Mandarin-speaking provinces, so far as we can get it,
noting, of course, as such, the words and phrases we know to
be local. Further, let it include as a prominent feature all sorts
of ready-made idiomatic phrases, and in general all
combinations of two or more characters in which the meaning
coalesces, or varies from the simple rendering of the separate
characters.
Considerable preliminary work had already been done, when the

death of Mrs. Goodrich compelled her husband to withdraw from the
partnership; and the project was abandoned by Mateer, though with
a hope that it might be resumed. In 1900, however, as the fruit of this
and kindred studies he published an analysis of two thousand one
hundred and eighteen Chinese characters. This little book was
designed to help children in dictation exercises to write characters,
and is still largely used for this purpose by mission schools. The
huge dictionary, though never completed, had three direct
descendants. With Dr. Goodrich it produced first a Chinese phrase
book, and then a pocket Chinese-English dictionary, which for brevity
and comprehensiveness is a marvel, and which is regarded by
almost every student of Chinese as a necessity. In marked contrast
with these two volumes is an immense dictionary left behind in
manuscript by Dr. Mateer. It is wholly in Chinese; and as it lies
unfinished it occupies more than a cubic foot of space, and consists
of a set of volumes. No comprehensive dictionary of the Chinese
language has been published for two hundred and fifty years, and
the last issued had been mainly classical. The object of this was to
supply the evident need of a great new work of that sort. One
insurmountable difficulty encountered was a phonetic arrangement
commanding common usage. None had the requisite approval.
Fortunately, on this undertaking Dr. Mateer did not spend his own
time, except so far as that was necessary to direct the preparation of
it by his scribes when they were not otherwise employed.
In his letter to his college classmates in 1897 he says that he has
“well in hand a work on electricity, and one on homiletics prepared
when teaching theology.” Neither of these was finished and
published. To his college classmate, S. C. T. Dodd, Esq., he wrote in
1898 that he was trying also to finish a work on moral philosophy. In
March, 1878, he wrote to Dr. W. A. P. Martin, of Peking: “You will
remember probably that when you were here I spoke of my intention
to make a natural philosophy by and by. You said, ‘Go ahead,’ and
that you would retire in my favor by the time mine was ready, say, ten
years hence. If I am spared I hope to have the book ready within the
time, if not sooner. As you know, natural philosophy is my hobby, and
I have taught it more thoroughly probably than has been done in any
other school in China. I intend when I visit America to prepare myself
with the material and the facilities for such work.” He was not able to
find time for this work; and when later Dr. Martin invited him to write
for the revised edition of his treatise the chapter on electricity, this
privilege had for the same reason to be put aside. He had also
advanced far toward the completion of a translation of “Pilgrim’s
Progress” into Mandarin.
His “Mandarin Lessons” was published early in 1892, and
immediately commanded a success even larger than its author may
have anticipated. Ever since, it has gone on toward a more general
use by foreigners wishing to master the language, and has now far
outstripped every other work of its kind. He was a quarter of a
century in making the book. June 28, 1873, he made the following
entry in his Journal concerning it:
Most of last week and this I have spent in making lessons

and planning a much larger number than I have made. Mr.
Mills urged me to work at them for Dr. ⸺’s benefit, as he did
not seem to take hold of Wade. I did not think of what a job I
was sliding into when I made three lessons for Maggie a few
years ago. I have now laid out quite an extensive plan, and if I
am spared I trust I shall be able to finish it, though it will take
a deal of work. I believe that I can produce a far better book
than any that has yet been brought forth. I was not intending
to do this work now, and cannot work much more at it, as
other matters imperatively demand attention.
Guided by the hint in this quotation, we are able to trace the book
still farther back to its very beginning. June 20, 1867, he said in his
Journal: “Maggie Brown [Julia’s sister] has been pushing on pretty
lively with the Chinese. I made her lessons for a good while, which
she studies, and now she is reading ‘The Peep of Day.’ I tried to
make her lessons with a view to bringing out the peculiarities of
Chinese idiom. It led me to a good deal of thinking and investigating.
I have a mind to review and complete the work, and may some day
give it to the world. My great difficulty is in classifying the results
attained.”
As the years went by his ideas of the plan for the work took
definite shape. In one of his letters concerning it he wrote:
Each lesson illustrates an idiom, the word idiom being

taken with some latitude. The sentences, as you will see, are
gathered from all quarters, and introduce every variety of
subjects. I have also introduced every variety of style that can
be called Mandarin, the higher style being found chiefly in the
second hundred lessons. The prevailing object, however, is to
help people to learn Mandarin as it is spoken. I have tried to
avoid distinct localisms, but not colloquialisms. A large
acquaintance with these is important, not to say essential, to
every really good speaker of Mandarin. It is, of course,
possible to avoid the most of them, and to learn to use a
narrow range of general Mandarin which never leaves the
dead level of commonplace expressions, except to introduce
some stilted book phrase. This, however, is not what the
Chinese themselves do, nor is it what foreigners should seek
to acquire. Many colloquialisms are very widely used, and
they serve to give force and variety to the language,
expressing in many instances what cannot be expressed in
any other way. I have tried to represent all quarters, and in
order to do so I have in many cases given two or more forms.
In the pursuit of his plan he sought the aid of competent scholars

in the north and in central China, so as to learn the colloquialisms
and the usage of words; also in the preparation of a syllabary of the
sounds of characters as heard in each of the large centers where
foreigners are resident. To accomplish this he also traveled widely.
Late in 1889, after a summer spent in studying the dialects of China,
he, in company with Julia, made a three months’ trip to the region of
the Yangtse, going down on the Grand Canal, spending a month on
the great river, and remaining a month at Nanking; always with the
main purpose of informing himself as to the current Mandarin, so as
to perfect his book. This tour enabled him to give it the final revision;
and in his opinion it “more than doubled the value” of the “Lessons.”
As finished, they were a huge quarto of six hundred pages, which
with the help of Mrs. Julia Mateer he saw through the press down at
Shanghai. In 1901, assisted by Mrs. Ada Mateer, he issued a more
elementary work of the same general nature.
The protracted study and care which he put upon the “Lessons”
were characteristic of him in all his literary productions. Upon this
subject no one is better qualified to bear testimony than is Dr.
George F. Fitch, Superintendent of the Presbyterian Mission Press,
at Shanghai, who speaks from direct personal observation. He says:
One very marked characteristic of Dr. Mateer was the

almost extreme painstaking with which he went over any work
which he was getting ready for publication; revising and re-
revising, seeking the judgment of others, and then waiting to
see if possibly new light might dawn upon the subject. I
remember reading shortly after I came to China the
manuscript of a paper which he had prepared with great labor,
upon the much-mooted “term question”; and in which he had
collected, with infinite pains, seemingly a great number of
quotations from the Chinese classics and other native works,
bearing on the use of Shen as the proper word for God in
Chinese. I urged him to publish at once, as I thought it might
be useful in helping settle that question. But he stoutly
refused, saying that it was not yet complete. Nor did it finally
see the light, in print, until nearly twenty years afterward.
None of his books at all reveal the protracted and toilsome

process of the preparation. We see only the result of years of
research. For instance, in his library there was a long row of Chinese
books each one of which showed a large number of little white slips
at the top. Each one of this multitude of marks had been placed
there by some student whom he had employed respectively to read
works in Chinese likely to use the word Shen, in order to indicate the
passages at which he needed to look. All these were canvassed,
and the different shades of meaning were classified.
From the “Mandarin Lessons,” and recently from the arithmetic, he
received substantial pecuniary returns, though not at all sufficient to
entitle him to be regarded as wealthy. In his manner of living he
would have been untrue to his training and impulses if he had not
practiced frugality, economy, and simplicity. As the means came into
his possession he used them generously both for personal friends
and for the promotion of the cause to which he had consecrated his
life. Of his outlays for the school and college we shall presently need
to speak. The expenses of the Yangtse trip came out of his own
pocket. March 9, 1895, he wrote to one of the secretaries of the
Board:
The mission minutes spoke, if you remember, of my

intention to erect a building for a museum and public lecture
room, and present it to the Board. This I intend to do at once.
It will cost about twelve hundred dollars, possibly more. I may
say in the same connection also that my “Mandarin Lessons”
has fully paid all the cost of printing, and so forth, and I expect
during the next year to pay into the treasury of the Board one
thousand dollars, Mexican. This I do in view of the liberality of
the Board in giving me my time while editing and printing the
book. When the second edition is printed I expect to pay over
a larger amount. I need not say that I feel very much gratified
that the book has proved such a success: especially do I feel
that it has been, and is going to be, very widely useful in
assisting missionaries to acquire the Chinese language. My
scientific books are also paying for themselves, but as yet
have left no margin of profits.
May 20, 1905, he wrote to a secretary: “I may say, however, that in

view of the great importance of the school both to the Tengchow
station and as a feeder to the college at Wei Hsien, I have set apart
from the profit of my ‘Mandarin Lessons’ enough to support the
school for the present year.” December 13, 1906, he wrote to a
friend in the United States: “My brother is now holding a large
meeting of elders and leading men from all the stations in this field.
There are about three hundred of them. It is no small expense to
board and lodge so many for ten days. I am paying the bill.” In one of
his latest letters to me he mentions this ability pecuniarily to help as
affording him satisfaction.
X
THE CARE OF THE NATIVE CHRISTIANS
“The need of the hour in China is not more new stations with expensive
buildings and wide itinerating. It is rather teaching and training what
we have, and giving it a proper development. Most of all we should
raise up and prepare pastors and preachers and teachers, who are
well grounded in the truth, so that the Chinese Church may have wise
and safe leaders.... There are already enough mission stations, or
centers, in the province, if they were properly worked. The need of the
hour is to consolidate and develop what we have, and by all means in
our power develop native agency, and teach and locate native
pastors,—men who are well grounded in the faith.”—letter to
secretary fox, of the American Bible Society, January 6, 1906.
Dr. Mateer believed that sooner than most missionaries

anticipated the Chinese Christians will join together and set up an
independent church. He meant by this not merely a union of the
ministers and churches of the various Presbyterian denominations at
work in the country, such as has already been effected, but an
organization that would include in its membership all the Protestant
Christians, and that would leave little or no place for the service of
foreign missionaries. He regarded this as inevitable; and for that
reason he considered it to be of prime importance that such an
effective preliminary work should promptly be done, that this coming
ecclesiastical independence might not be attended by unsoundness
as to creed or laxity in life. At the same time, in holding up the care
and the training of the native Christians as so important a part of the
work of the foreign missionary in China, in anticipation of what is
ahead, he was only for an additional reason urging what he had in all
his long career recognized as second to no other in importance. Of
course, at the beginning of the effort to give the gospel to a people it
is indispensable to do “the work of an evangelist”; that is, to seek by
the spoken word and by the printed book to acquaint them with
elementary Christian truth, and to endeavor to win them to Christ;
and we have already seen how diligent Dr. Mateer was in this
service, especially in his earlier missionary years. But he was just as
diligent in caring for the converts when gained; and in the school and
college it was the preparation of men for pastors and teachers and
evangelists that was constantly his chief aim.
The first body of native Christians with whose oversight he had
anything to do was that very small band that had been gathered into
the church at Tengchow. Mills was the senior missionary, and as
such he presided over that little flock until his death. In 1867 he was
installed as the pastor, and he continued in this office nearly twenty
years. During this long period Dr. Mateer at times supplied the pulpit
and cared for the church in Mills’s absence or illness, but for most of
the time it was only as a sort of adviser that he could render help in
that field. We have no reason to think specially unfavorably of
Chinese converts because some of those with whom he then had to
do at Tengchow, or elsewhere, proved themselves, to him, to be a
discouraging set of professing Christians. Were not a good many of
Paul’s converts very much of the same grade when he traveled
among the churches, and wrote his letters? Did it not take much
patience, and fidelity, and persistence on the part of Christ to make
anything worth while out of his select disciples? Yet these constituted
the membership of the primitive church from which even the
missionaries of our day have originated. At any rate some of the
earliest experiences of Dr. Mateer with the native Christians were of
a very depressing sort. In his Journal, under date of March 17, 1864,
he made this record:
Since coming to Tengchow there have been great

difficulties in the native church. Several of the members were
accused by common fame of various immoral practices,—one
of smoking opium, another of lying and conforming to
idolatrous practices, and another of breaking the Sabbath.
The second of these confessed his fault, and was publicly
reproved; the third also confessed, and on his profession of
penitence was restored to the confidence of the church. But
though the first confessed to the use of the ashes of opium,
he gave no certain assurance of amendment; and he was
suspended, and so remains. These matters gave us all a
great deal of anxiety and sorrow of heart. It is sad thus to find
that even those who profess the name of Christ are so much
under the power of sin. It is one of the great discouragements
of the missionary work. Yet God is able to keep even such
weak ones as these unto eternal life.
Under date of September 15, 1866, he told of a worse case of

discipline:
We had a hearing with the accused, and gave him notice

that he would be tried, and of the charges and witnesses. We
wrote to Mr. Corbett at Chefoo, to get depositions for us. He
did so, and we met, and tried him. The evidence was
sufficient to convict him of lying, and of forging an account,
and of adultery; notwithstanding, he denied it all, endeavoring
to explain away such evidence as he was forced to admit. We
decided to excommunicate him, and it was done two weeks
ago.
It must not be supposed that there was a great deal of such

discouraging work; as a rule, the native Christians tried to live correct
lives; and the worst that could be said of most of them at those early
dates was that they were “babes” in Christ. But we cannot appreciate
what the missionary needs to do as to the professed converts unless
we look at this depressing phase. Besides, incidentally we are thus
shown one of the methods by which the native Christians were
trained in the conduct of their own churches. Each case is dealt with
just as is required by the regulations of the denomination with which
the church is associated. The same formalities and processes are
employed as if in the United States; the same fairness and fullness
of investigation, with witnesses and hearing of the accused; and the
same effort neither to fall below nor to exceed what justice and
charity combined demand for the good of the individual and of the
organization as a whole. As to this, in these particular cases no
exceptional credit can be claimed for Dr. Mateer; but we can be
perfectly sure that it commanded his hearty approbation. This was a
practical school also in which was called into exercise a quality of
which a young missionary, and especially a man of his type, seldom
has enough,—that of mingling a firm adherence to truth and
righteousness with a forbearing kindness that will not break a
bruised reed or quench the smoking flax. Gradually this became so
characteristic of him that the boys in his school and the Christians in
the churches were accustomed to come to him and unburden
themselves not only of sorrows, but of faults, with no expectation that
he would condone wrong or shield them from its just consequences,
but confident that he would feel for them, and help them if he could.
Nor was it to these classes alone that his heart and hands opened.
As they came to know him better, the professor in the imperial
university sought his advice and the coolie turned to him in his need;
and never in vain.
But there was a brighter side to the experience of those early
days. Several of the boys in the school were converted. What joy this
afforded, we who live in Christian lands cannot appreciate. The little
church at Tengchow also steadily moved forward in those early days
of its history. In 1869 it had risen to about fifty members, and the
attendance was such that a building solely for its services became
indispensable; and in due time an appropriation was made by the
Board of Missions, first for a lot, and soon after for a house of
worship. Pastor Mills was then absent, and by appointment of
presbytery Dr. Mateer acted as stated supply. As such, having first
bought the lot, he made an appeal to the Board for the new edifice,
saying:
We hold our services in the boys’ schoolroom, which has

been kept inconveniently large, for this very purpose. It is the
only room that will seat all, and it will not do it sometimes. The
desks have to be carried out every Sabbath; and all the
benches, chairs, and so forth, about the establishment carried
in, making a decidedly nondescript collection. Aside from the
inconvenience, two serious drawbacks are felt. One is the
want of sacred associations about the place. All heathen are
wanting in reverence, and no small part of what they need is
to have this idea instilled into their minds. We greatly need in
this work a house especially devoted to the worship of God.
The other drawback is the disorganizing effect the Sabbath
and week-day services have on the school. The room being in
the midst of the premises, it is impossible to prevent a large
amount of lounging, gossiping, and so forth, in the boys’ room
before the service begins. The superintendent feels that it is a
very serious drawback to the school, as well as an injury to
the native Christians.
Any American who is familiar with students and their habits will
perceive that in this matter Chinese young men and boys are very
much like those of our own land.
In that appeal there is another paragraph that deserves
transcription here:
It has been said that the Christians in heathen lands ought

to build their own churches, but this is impossible in the early
stages of the work, especially at the center of operations,
where the foreigner preaches and teaches in person, and
where a large part of his hearers are often from a distance.
The church at this place gives character to the whole work in
the eyes of the people at large, and must of necessity differ in
many respects from churches in small places presided over
by native pastors. Concerning these last we have already
taken a decided stand, requiring the natives to help
themselves to a great extent.
Dr. Mateer was appointed by the presbytery to serve a second

year as stated supply of the Tengchow church; and had it not been
that he was called in 1870 to Shanghai to take charge of the mission
press, he no doubt would have given his personal supervision to the
erection of the new house of worship. It was built during his absence,
and when he came back he rejoiced in its completion. At the death of
Mills in 1895, Dr. Mateer was chosen pastor, and was installed as
such,—a position he was able to assume because he had found in
Mr. Hayes a substitute for himself in the presidency of the college.
He remained pastor until he went with the college to Wei Hsien. Dr.
Hayes had already for years worked quietly and efficiently in the
school, under the presidency of Dr. Mateer, and had shown himself
to be a man of exceptional ability and energy—a man after Dr.
Mateer’s own heart. After he assumed the presidency Dr. Mateer
was still to assist in the college, but he was so often absent or
otherwise engaged that both the college and the preaching were
largely in the hands of Dr. Hayes.
According to the “Form of Government” of the Presbyterian
Church in the United States of America, when a “call” is made out for
a pastor it must be certified to have been voted by a majority of the
people entitled to exercise this right; and it must fill the blank in the
following clause: “And that you may be free from worldly cares and
avocations, we hereby promise and oblige ourselves to pay to you
the sum of ... in regular quarterly (or half-yearly, or yearly) payments
during the time of your being and continuing the regular pastor of this
church.” In the settling of native pastors over the Chinese churches
scattered through the country, the filling of that blank, and the actual
subscription of the funds needed for this and other expenses of the
organization, usually require the presence of a missionary and of his
earnest stimulation and guidance. Sometimes the pledges are very
liberal, if estimated by ability of the members; and sometimes it is
with great difficulty that they are brought up to the measure of their
duty. The salaries, however, are almost incredibly small, and even
according to Chinese standards are scarcely sufficient for a
livelihood. We need to keep this state of things in mind in order to
appreciate the amount that was inserted in the blank in Dr. Mateer’s
call to the pastorate of the Tengchow church. In reporting the entire
procedure to the Board of Missions, he said: “The church in
Tengchow in calling me for their pastor promised a salary of cash
amounting to fifty dollars, which is to be used to employ an
evangelist whom I am to select and direct.” Of course, he continued
to receive his own pay as a missionary from the funds of the Board.
The fifty dollars was probably a creditable amount, as contributed by
the native members out of their narrow means; and as a salary for a
native evangelist it was at least a fair average.
When reporting this pastorate to the Board of Missions, Dr. Mateer
said, “This is work that I love to do, especially the preaching.” When
doing the work of an evangelist among the people at large,
sermonizing could have no place. Even formal addresses of any sort
were rarely practicable. The best that the missionary can do when
itinerating is to get attention by any legitimate means, and then to
talk, and hear and answer questions, and bear with all sorts of
irrelevancies and interruptions. But when a church is organized, a
sermon, consisting of a passage of Scripture and a discourse built
upon it, is just as much in place as it is in one of our home houses of
worship on the Sabbath. It was to the opportunity for that form of
service that he refers when he expressed his pleasure in the
pastorate. In this also he greatly excelled. Some who knew him most
intimately, and who appreciated fully his great worth and efficiency,
did not regard him as a very eloquent preacher in an English pulpit.
He commanded the attention of his audience by his strong, clear,
earnest presentation of the great religious truths which he believed
with all his soul. The personality and consecration of the man were a
tremendous force when he stood in a pulpit in his own land; what he
lacked was the ability which some speakers possess of carrying his
audience with him, almost irrespective of the thoughts to which they
give utterance. But in preaching to the Chinese he took on an
extraordinary effectiveness. There was in the man, in the movement
of his thought, in his mastery of the language, in the intense
earnestness of his delivery, in the substance of his sermons and
addresses, much that captivated the native Christians, and made
others bow before his power. Mr. Baller, who had heard him
frequently, says: “His sermons were logical, direct, a unit in thought
and enriched with a copious vocabulary and illustrations. His points
were usually put from the Chinese point of view, so that a foreign air
was conspicuously absent.” To this day some of his addresses are
recalled as triumphs of real eloquence of speech; perhaps the most
notable of these being an address which he delivered at the opening
of the English Baptist Institution at Tsinan fu, in 1907. It was an

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ISBN 978-3-030-37315-3 ISBN 978-3-030-37317-7 (eBook)

© Springer Nature Switzerland AG 2020

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He consented to manage the press only until a competent man

I am not in favor of enlargement, but I would be very sorry

It is the result of much pains and labor.... The book is

The book was published the following year. To the same

My idea of the book is a dictionary of the spoken language

Considerable preliminary work had already been done, when the

Most of last week and this I have spent in making lessons

Each lesson illustrates an idiom, the word idiom being

In the pursuit of his plan he sought the aid of competent scholars

One very marked characteristic of Dr. Mateer was the

None of his books at all reveal the protracted and toilsome

The mission minutes spoke, if you remember, of my

May 20, 1905, he wrote to a secretary: “I may say, however, that in

Dr. Mateer believed that sooner than most missionaries

Since coming to Tengchow there have been great

Under date of September 15, 1866, he told of a worse case of

We had a hearing with the accused, and gave him notice

It must not be supposed that there was a great deal of such

We hold our services in the boys’ schoolroom, which has

It has been said that the Christians in heathen lands ought

Dr. Mateer was appointed by the presbytery to serve a second

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