DEVELOPMENT

OF
PERIODONTIUM
CONTENTS:
 Cementum
 Formation of cementum
 Periodontal ligament
 Alveolar bone
 Gingiva

DEPT. OF ORAL PATHOLOGY 01/18/2024 2

 Diagrammatic representation of developing tooth bud in cap stage
Source: Cho MI, Garant PR. Development and general structure of the periodontium. Periodontol 2000. 2000 Oct;24:9-27. doi: 10.1034/j.1600-0757.2000.2240102.x. PMID: 11276876.

DEPT. OF ORAL PATHOLOGY 01/18/2024 3

CEMENTUM

 A hard, avascular connective tissue that covers

roots of teeth
 Acellular and Cellular
 Extrinsic fiber and Intrinsic fiber

Source: Ten Cate’s Oral Histology_ Development, Structure, and Function

DEPT. OF ORAL PATHOLOGY 01/18/2024 4
Histologic sections of the advancing root edge in (A) a rat during acellular extrinsic fiber cementum (AEFC) formation an
(B) a human during cellular intrinsic fiber cementum (CIFC) formation
Source: Ten Cate’s Oral Histology_ Development, Structure, and Function

DEPT. OF ORAL PATHOLOGY 01/18/2024 5

CEMENTUM FORMATION (CEMENTOGENESIS)
 Progresses through 3 sequential stages: 1. Fibrillogenesis
2. Matrix maturation
3. Mineralisation

Bilaminar layer of cuboidal/low columnar epithelial cells forms (HERS)

Sends inductive message to facing ectomesenchymal pulp cells

These cells differentiate into odontoblasts and deposit predentine

Fibrous and cellular component
Rearrangement of abutting HERS components of dental follicle increase in
quantity
Continuity disrupted,
components of dental Reciprocal inductive signal HERS cells
follicle come in contact from dentine/HERS to transform into
DEPT. OF ORAL PATHOLOGY 01/18/2024 6
with calcifying dentine infiltrating follicle cells cementoblasts
 Epithelial rest cells of Malassez form
First, collagen elements migrate and forms initial matrix

Cementoblasts align, differentiate and acquire full functional

competency

Cementoblasts produce intrinsic fibres

Precementum/Cementoid
forms

Calcification of cementum matrix

(Crystal nucleation, organization, orientation and growth)
Initial increment of cementum with
epithelial cell rests of malassez
An intact, uninterrupted cementogenic layer is formed

DEPT. OF ORAL PATHOLOGY 01/18/2024 7

Cementogenesis in apical third of root does not follow these
sequential steps

Specific areas mineralise out of sequence

Cementoblasts become entrapped in calcifying

environment

Entrapped cementoblasts differentiate into

cementocytes

Developing root at cemento-enamel junction

DEPT. OF ORAL PATHOLOGY 01/18/2024 8
Source: Oral histology inheritance and development Provenza
COMPOSITION OF CEMENTUM

 Collagen (type 1,3 and 12)

 Non collagenous proteins (Bone Sialoprotein, Osteopontin, Gla proteins, Osteocalcin,
Osteonectin, Alkaline phosphatase, Cementum specific proteins
 Glycoproteins (Chondroitin sulphate, Hyaluronic acid, Dermatan sulphate, Keratan
sulphate) and water

DEPT. OF ORAL PATHOLOGY 01/18/2024 9

BONE SIALOPROTEIN AND OSTEOPONTIN

 Matrix proteins with cell adhesion motifs (arginine-glycine-glutamic acid)

 Promotes adhesion of selected cells to newly formed root surface
 Balance between them contribute to maintain unmineralized PDL between 2
mineralized tissues

DEPT. OF ORAL PATHOLOGY 01/18/2024 10

GLA PROTEINS

 Matrix ɣ-carboxyglutamic acid & Osteocalcin

 Calcium binding amino acid, regulates extent of mineralisation
 Marker for maturation of osteoblasts, cementoblasts & odontoblasts
 MGP: acts as inhibitor of mineralisation, preserves PDL width

DEPT. OF ORAL PATHOLOGY 01/18/2024 11

BONE MORPHOGENETIC PROTEINS

 BMP-2,4,7
 Part of epithelial-mesenchymal signaling molecules
 Promote differentiation of preosteoblasts and cementoblasts precursors
 Promote expression of Runx-2
 Used successfully in periodontal regeneration

DEPT. OF ORAL PATHOLOGY 01/18/2024 12

TRANSCRIPTION FACTORS

 Runx-2 (runt related transcription factor-2) or cbfa-1

 Osterix
 Master switches for differentiation of osteoblasts
 Now, found expressed in follicle cells, PDL cells & cementoblasts

DEPT. OF ORAL PATHOLOGY 01/18/2024 13

WNT SIGNALING

 Glycoproteins acting extracellularly, regulates development, growth, patterning

 Wnt: Cementoblast proliferation

 Antagonist: sclerostin

DEPT. OF ORAL PATHOLOGY 01/18/2024 14

ALKALINE PHOSPHATASE

 Hydrolyses pyrophosphatase, inhibits the inhibition of hydroxyapatite formation

 Deficiency: complete absence of acellular and cellular cementum, permanent tooth
loss

DEPT. OF ORAL PATHOLOGY 01/18/2024 15

CEMENTUM DERIVED GROWTH FACTOR
• Protein homologous to insulin like growth factor-1
• Accounts for 70% of mitogenic activity of cementum (Nakae at al)
• Induces signaling pathways: activation of protein kinase C cascade, increased
concentration of cytosolic calcium, expression of cellular proto-oncogenes

Serve as storage site for growth inducing molecules

Promotes migration and growth of progenitor cells in adjacent structures

Thus, serve a biological role in promoting periodontal regeneration

DEPT. OF ORAL PATHOLOGY 01/18/2024 16

CEMENTUM ATTACHMENT PROTEINS

 Localised exclusively in cementum

 Binds to hydroxyapatite in cementum with high affinity
 Promotes attachment of osteoblastic cells > PDL cells > gingival fibroblasts,
endothelial cells & smooth muscle cells

DEPT. OF ORAL PATHOLOGY 01/18/2024 17

CEMENTUM PROTEIN 1

 Maps to chromosome 16p13.3

 247 amino acid sequence
 Mol wt.-26kDa
 Regulates crystal growth and composition of apatite crystals

DEPT. OF ORAL PATHOLOGY 01/18/2024 18

Source: Arzate H, Zeichner-
David M, Mercado-Celis G.
Cementum proteins: role in
cementogenesis,
biomineralization,
periodontium formation and
regeneration. Periodontol 2000.
2015 Feb;67(1):211-33. doi:
10.1111/prd.12062. PMID:
25494602.

Scanning electron micrograph images of crystal growth. (A) Human recombinant cementum protein-1 induced formation of sphere with irradiating prismatic crystals. (B) Enlargement of the box in
panel A shows the octacalcium phosphate prismatic crystals. (C) The internal part of the sphere shows a central nucleus with irradiating prismatic crystal. (D) A more detailed view of the box in
panel C shows that the irradiating crystals are originating from a central nucleus in a needle-like shape that later acquires the prismatic crystal morphology that grows only in cementum protein-1-
containing gels DEPT. OF ORAL PATHOLOGY 01/18/2024 19
 PERIODONTAL LIGAMENT
 Soft, specialized connective tissue
 0.15 – 0.38 mm in width (thinnest in middle)
 Supports teeth in their socket
 Helps withstand considerable forces of
mastication
 Acts as sensory receptor (necessary for
proper positioning of jaws during
mastication)

Schematic overview of principal fibres of PDL

DEPT. OF ORAL PATHOLOGY 01/18/2024 20

 FORMATION
• Develops from dental follicle
• Formation starts at cemento-enamel junction (CEJ) & progresses in apical direction
• Formation occurs from mineralized surface towards PDL proper
• It occurs on tooth side first along with formation of cementum
• When root and PDL start to develop, alveolar bone is already mineralized, but still
remains subjected to extensive remodelling. This contributes to binding of sharpey’s fibres
to bone matrix  Escape mineralization
 Osteoid matrix
 Resorption pits

DEPT. OF ORAL PATHOLOGY 01/18/2024 21

 Sharpey’s fibres from cementum and bone differ in size and number
de Jong T, Bakker AD, Everts V, Smit TH. The intricate anatomy of the periodontal ligament and its development: Lessons for periodontal regeneration. J Periodontal Res. 2017 Dec;52(6):965-974
doi: 10.1111/jre.12477. Epub 2017 Jun 21. PMID: 28635007.

DEPT. OF ORAL PATHOLOGY 01/18/2024 22

 During formation of sharpey’s fibres, PDL space contains loosely arranged collagen fibrils
and precursor cells

As PDL development starts, fibroblasts produce new extracellular matrix and shape
existing structures

Remodelling at both ends of sharpey’s fibres occur

PDL fibres grow by lateral and longitudinal apposition of fibrils

Growing collagen fibre bundles form anastomosing network

DEPT. OF ORAL PATHOLOGY 01/18/2024 23

 PRE EMERGENCE STAGE

Root formed is one-third

At CEJ: Fibres from cementum
follow outline of crown
Middle: fibres emerge and are
perpendicular to long axis of
tooth
Periapical: Fibres near cementum
and bone are densely packed

DEPT. OF ORAL PATHOLOGY 01/18/2024 24

Source: de Jong T, Bakker AD, Everts V, Smit TH. The intricate anatomy of the periodontal ligament and its development: Lessons for periodontal regeneration. J Periodontal Res. 2017
Dec;52(6):965-974. doi: 10.1111/jre.12477. Epub 2017 Jun 21. PMID: 28635007.
 PRE OCCLUSAL STAGE

Dentogingival Fibres: Mature,

follow enamel surface from
cementum to interproximal
gingiva
Transseptal fibres: run in
oblique-apical/superior-oblique
direction
Coronal and cervical part:
Organised fibres seen
Middle third: brush-like fibres
emerging form both ends

DEPT. OF ORAL PATHOLOGY 01/18/2024 25

Source: de Jong T, Bakker AD, Everts V, Smit TH. The intricate anatomy of the periodontal ligament and its development: Lessons for periodontal regeneration. J Periodontal Res. 2017
Dec;52(6):965-974. doi: 10.1111/jre.12477. Epub 2017 Jun 21. PMID: 28635007.
 FIRST OCCLUSAL CONTACT

Dentogingival and
transseptal fibres are well
developed
Cervical third: fibers run
obliquely downwards
from cementum to
alveolar bone
Midroot to apical third:
thick fibres from alveolar
bone and thin fibres from
cementum extend into
PDL space. No
interwining seen.

DEPT. OF ORAL PATHOLOGY 01/18/2024 26

Source: de Jong T, Bakker AD, Everts V, Smit TH. The intricate anatomy of the periodontal ligament and its development: Lessons for periodontal regeneration. J Periodontal Res. 2017
Dec;52(6):965-974. doi: 10.1111/jre.12477. Epub 2017 Jun 21. PMID: 28635007.
 FULL OCCLUSAL CONTACT

Interwined network of
fibres present
All principal fibres seen
Central zone absent
Fibres on cementum side
thicken on occlusal
loading

01/18/2024 27
Source: de Jong T, Bakker AD, Everts V, Smit TH. The intricate anatomy of the periodontal ligament and its development: Lessons for periodontal regeneration. J Periodontal Res. 2017
Dec;52(6):965-974. doi: 10.1111/jre.12477. Epub 2017 Jun 21. PMID: 28635007.
 Change in orientation of PDL fibres from pre-occlusal to occlusal stage

DEPT. OF ORAL PATHOLOGY 01/18/2024 28

Source: de Jong T, Bakker AD, Everts V, Smit TH. The intricate anatomy of the periodontal ligament and its development: Lessons for periodontal regeneration. J Periodontal Res. 2017 Dec;52(6):965-974. doi: 10.1111/jre.12477. Epub
2017 Jun 21. PMID: 28635007.
DEVELOPMENT OF PERIODONTAL LIGAMENT
Timing Connective tissue fibroblasts
surrounding root
Before eruption Loose & unstructured Quiescent

Approaching subjacent Density increases, PDL Active

mucosa fibres seen without
orientation
Upon eruption Obique orientation; Align in oblique
alveolar crest fibres are direction to long axis of
formed tooth
First occlusal contact Horizontal group of
fibres completely
develop
Definitive occlusion Oblique group of fibre
established bundles develop

DEPT. OF ORAL PATHOLOGY 01/18/2024 29

Magnitude and Direction of strain directs PDL fibroblasts
to remodel PDL fibres
• When increased occlusal load: PDL width increases and thickness of fibre bundles
increase, bony trabeculae increase in number and thickness, alveolar bone thickens
• Reduction in occlusal load: PDL width decreases, fibre bundles decrease in number ad
thickness, trabeculae become fewer, deposition of additional cementum occurs

DEPT. OF ORAL PATHOLOGY 01/18/2024 30

SIGNALING MOLECULES: PDL
 Transcription factors

 Homeobox genes – Msx1, Msx2, Dlx1, Dlx2, Dlx3, Otlx2,Barx1

 Pax genes – Pax9, Pax6

 Lef1, Gli2/Gli3,Shh,Nfi-c

 Growth factors - TGFβ1 & 2, BMP2, 3, 4, &7, Activin, FGF 4,8 & 9, Hepatocyte
growth factor, IGF1

DEPT. OF ORAL PATHOLOGY 01/18/2024 31

ALVEOLAR BONE
 Tooth dependent structure: size, shape, location and
function of teeth determine its morphology
 Parts: Alveolar bone proper

: Central spongiosa
: Buccal and lingual cortical plates
 Growth begins with completion of crown & beginning
of root formation
 Intramembranous formation (loose connective tissue as
primordium)
 Formation is not a continuous process
 Quiescent periods: Intense, darkly stained lines called
resting lines

DEPT. OF ORAL PATHOLOGY 01/18/2024 32

 DEVELOPMENT OF ALVEOLAR BONE
Alveolar process is defined as the part of the maxilla and the mandible that form and support the socket
of teeth

Late bell stage: Bony septa and bony bridge start to form and separate tooth germs

Individual tooth germs lie in clearly outlined bony compartment

In bony compartments (prior to tooth formation), tooth germs show continued bodily movement to
adjust to growing jaws

With development of roots; alveolar process increase in height, cells in dental follicle differentiate
into osteoblasts and form alveolar bone proper

DEPT. OF ORAL PATHOLOGY 01/18/2024 33

 SIGNALING MOLECULES: ALVEOLAR BONE
 Cbfa1 gene (induced by BMP7): Master gene for mesechymal cell differentiation into osteogenic cell lines

 Transcription factors

 Cbfa1 protein: Transcription factor for osteocalcin, osteopontin, BSP, and collagen
 AP -1(Activating factor -1) produced by the association of protein encoded by C-fos and C-jun genes

 BMPs- BMP 2,3,4,6 and 7: Bone inductive activity

 BMP 2: Chemoattractent to osteoblast

 BMP 7: Proliferation and differentiation
 FGF- increases the proliferation and differentiation of osteogenic cells

 Colony stimulating factors- Granulocyte-Macrphage CSF stimulate osteoblast, Monocyte CSF stimulate
preosteoclast differentiation
 PDGF- Chemotactic and mitogenic factor for osteoblastic cells

 IGF and
DEPT. TGF-β-
OF ORAL Stimulate osteoblast
PATHOLOGY 01/18/2024 34
DEVELOPMENT OF GINGIVA
Gingiva: Part of masticatory mucosa which covers the alveolar process and surrounds the
cervical portion of tooth
Gingival epithelium: Ectodermal origin
Oral epithelium – develop from oral mucosal epithelium
Sulcular epithelium - develop from oral mucosal epithelium
Junctional epithelium – develop from REE
Gingival connective tissue – mesodermal in origin

DEPT. OF ORAL PATHOLOGY 01/18/2024 35

DEPT. OF ORAL PATHOLOGY 01/18/2024 36
SHIFT OF DENTO GINGIVAL JUNCTION

• First stage – bottom of the gingival sulcus remains in the region of the enamel covered
crown and apical end of the attachment epithelium stays at cementoenamel junction .
• Second stage – bottom of gingival sulcus is still on enamel and apical end of
attachment epithelium has shifted to cementum .
• Third stage – bottom of gingival sulcus is at cementoenamel junction, attachment
epithelium is completely on cementum . crown is fully exposed .
• Fourth stage – represents recession of gingiva . entire attachment is on cementum , the
gingiva may appear normal but have receeded as a result of pathology .

DEPT. OF ORAL PATHOLOGY 01/18/2024 37

DEPT. OF ORAL PATHOLOGY 01/18/2024 38
 OVERVIEW OF THE DEVELOPMENT

DEPT. OF ORAL PATHOLOGY 01/18/2024 39

Source: Ten Cate’s book of Oral Histology
 AGE CHANGES IN PERIODONTIUM

DEPT. OF ORAL PATHOLOGY 01/18/2024 40

 GINGIVA

 Homeostatic regulation negatively affected

 Fibroblasts show reduced capacity to proliferate and migrate
 Altered myofibroblastic differentiation
 Reduced collagen remodelling
 Increased anti-apoptotic and decreased pro-apoptotic gene expression (animal studies)

DEPT. OF ORAL PATHOLOGY 01/18/2024 41

Kim YG, Lee SM, Bae S, Park T, Kim H, Jang Y, Moon K, Kim H, Lee K, Park J, Byun JS, Kim DY. Effect of Aging on Homeostasis in the Soft Tissue of the Periodontium: A Narrative Review. J Pers Med. 2021 Jan
18;11(1):58. doi: 10.3390/jpm11010058. PMID: 33477537; PMCID: PMC7831085.
 PDL

 Reduced cell proliferation

 Reduced mineral nodule formation
 mRNA expression of type 1 & 3 collagen reduces
 Loss of c-fos expression, reduced activity of AP-1 transcription factor
 Increased pro-inflammatory genes: Osteoprotregrin, IL-1,6
 Reduced alkaline phosphatase activity

DEPT. OF ORAL PATHOLOGY 01/18/2024 42

Kim YG, Lee SM, Bae S, Park T, Kim H, Jang Y, Moon K, Kim H, Lee K, Park J, Byun JS, Kim DY. Effect of Aging on Homeostasis in the Soft Tissue of the Periodontium: A Narrative Review. J Pers Med. 2021 Jan 18;11(1):58. doi:
10.3390/jpm11010058. PMID: 33477537; PMCID: PMC7831085.
CEMENTUM

 Thickness increses (more in apical region)

 Increasingly acellular
 Increased areas of cementum resorption followed by apposition, irregular surface of
cementum

DEPT. OF ORAL PATHOLOGY 01/18/2024 43

ALVEOLAR BONE

 Reduced rate of bone formation

 Reduced width of cribriform plate
 Reduced width of interdental septum
 Reduction in cells of osteogenic layer of bone

DEPT. OF ORAL PATHOLOGY 01/18/2024 44

 DISORDERS AFFECTING PERIODONTIUM

DEPT. OF ORAL PATHOLOGY 01/18/2024 45

 HYPOPHOSPHATASIA

DEPT. OF ORAL PATHOLOGY 01/18/2024 46

Nunes ME. Hypophosphatasia. 2007 Nov 20 [Updated 2023 Mar 30]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023.
 DEPT. OF ORAL PATHOLOGY 01/18/2024 47
Okawa R, Nakano K. Dental manifestation and management of hypophosphatasia. Jpn Dent Sci Rev. 2022 Nov;58:208-216. doi: 10.1016/j.jdsr.2022.06.002. Epub 2022 Jul 2. PMID: 35814738; PMCID: PMC9260292 .
 DEPT. OF ORAL PATHOLOGY 01/18/2024 48
Okawa R, Nakano K. Dental manifestation and management of hypophosphatasia. Jpn Dent Sci Rev. 2022 Nov;58:208-216. doi: 10.1016/j.jdsr.2022.06.002. Epub 2022 Jul 2. PMID: 35814738; PMCID: PMC9260292.
 Hypercementosis

Lateral view: Skull showing excessive cementum

deposition around maxillary teeth with widened
and protruding maxilla

DEPT. OF ORAL PATHOLOGY 01/18/2024 49

Rao VM, Karasick D. Hypercementosis--an important clue to Paget disease of the maxilla.
Brad W. Neville, Douglas D. Damm, Carl M. Allen, Angela C. Chi - Oral and Maxillofacial Pathology (2015, Saunders)
Skeletal Radiol. 1982;9(2):126-8. doi: 10.1007/BF00360497. PMID: 7163823.
 Langerhans cell histiocytosis

Scooped out radiolucency seen in mandibular posterior region

DEPT. OF ORAL PATHOLOGY 01/18/2024 50

 Hyperparathryoidism

Generalised loss of lamina dura and ground glass appearance of bone: Hyperparathyroidism

DEPT. OF ORAL PATHOLOGY 01/18/2024 51

Kaffee I, Tamse A, Scheartz Y, Buchner A, Littner MM. Changes in the lamina dura as a manifestation of systemic diseases: report of a case and review of the literature. J Endod.
1982 Oct;8(10):467-70. doi: 10.1016/s0099-2399(82)80152-0. PMID: 6958785.
 Trabeculae of cellular woven bone and clusters of multinucleated giant cells within a background of
cellular fibrous connective tissue
DEPT. OF ORAL PATHOLOGY 01/18/2024 52
Brad W. Neville, Douglas D. Damm, Carl M. Allen, Angela C. Chi - Oral and Maxillofacial Pathology (2015, Saunders)
REFERENCES
 Ten Cate’s Oral Histology: Development, Structure and Function

 Oral histology inheritance and development Provenza

 Orban’s Oral Histology And Embrology, 12 th edition

 Arzate H, Zeichner-David M, Mercado-Celis G. Cementum proteins: role in cementogenesis, biomineralization,

periodontium formation and regeneration. Periodontol 2000. 2015 Feb;67(1):211-33. doi: 10.1111/prd.12062. PMID:
25494602
 de Jong T, Bakker AD, Everts V, Smit TH. The intricate anatomy of the periodontal ligament and its development: Lessons
for periodontal regeneration. J Periodontal Res. 2017 Dec;52(6):965-974. doi: 10.1111/jre.12477. Epub 2017 Jun 21. PMID:
28635007
 Okawa R, Nakano K. Dental manifestation and management of hypophosphatasia. Jpn Dent Sci Rev. 2022 Nov;58:208-216.
doi: 10.1016/j.jdsr.2022.06.002. Epub 2022 Jul 2. PMID: 35814738; PMCID: PMC9260292
 Rao VM, Karasick D. Hypercementosis--an important clue to Paget disease of the maxilla. Skeletal Radiol. 1982;9(2):126-8.
doi: 10.1007/BF00360497. PMID: 7163823
 Kaffee I, Tamse A, Scheartz Y, Buchner A, Littner MM. Changes in the lamina dura as a manifestation of systemic diseases:
report of a case and review of the literature. J Endod. 1982 Oct;8(10):467-70. doi: 10.1016/s0099-2399(82)80152-0. PMID:
6958785.
DEPT. OF ORAL PATHOLOGY 01/18/2024 53
 THANK YOU

DEPT. OF ORAL PATHOLOGY 01/18/2024 54