DEVELOPMENT OF HUMAN PERIODONTIUM

DR. SHEEJA .S. VARGHESE Saveetha dental college

Mammalian periodontium could be regarded as the most complex type of tooth attachment with regard to structure and function

Evolution of tooth attachment

ACRODONT

PLEURODONT

THECODONT

VARIATIONSVariations IN THECODONTAL in thecodontal ATTACHMENTS IN attachments MAMMALS inDEPENDS mammals ON

Form and function of teeth(homodont,hetrodont) Tooth replacement pattern (polyphidonty, monophydonty, diphidonty .semidiphidonty)

Eruption pattern (continuously growing, slow but continuous, no continuous eruption)

SIX GROUPS OF THECODONTAL PERIODONTIUM

Group-1 : incisors and canines of omnivores, herbivores, carnivores Group-2: premolars and molars of omnivores and carnivores Group-3 : premolars and molars of herbivores Group-4 : incisors of rodents , some molars of guinea pigs , rabbits Group-5: Dolphins and whales Group-6: some molars of rodents

FOR THE DEVELOPMENT OF HUMAN PERIODONTIUM

PRECURSER CELLS

SIGNALLING MOLECULES

INDUCTION , COMPETENCE, DIFFERENTIATION

PRECURSER CELLS

DENTAL ECTOMESENCHYME

ORAL EPITHELIAL CELLS

NEURAL CREST ORIGIN

ECTODERM OF 1ST PHARYNGEAL ARCH

NEURULATION & NEURAL CREST CELLS

EPITHELIAL MESENCHYMAL TRANSFORMATION OF NEURAL CREST CELLS

-by changing cytoskeletal organization and cell adhesive property. Molecular level changes in neural crest cells
1. Expression of snail zinc finger transcription factor family that suppress E cadherin 2. Expression of BMP protein and fibroblast growth factor signaling pathways

DERIVATIVES OF NEURAL CREST CELLS

PRIMITIVE ORAL CAVITY

BRANCHIAL(PHARYNGEAL) ARCHES

ORAL EPITHELIUM (1ST ARCH EPITHELIUM)

SIGNALLING MOLECULES
MORPHOGENS Differentiation & migration of cells thereby dictate morphology and function of developing tissues GROWTH FACTORS- Cellular proliferation ,migration and survival

TRANSCRIPTION FACTORS Homeodomain proteins , PAX proteins etc --Regulates gene transcription

NUCLEAR RECEPTORS -Steroid/ Thyroid/ retinoic acid super family --Hormone activated transcription factors

MORPHOGENS

TGF super family BMP, Activin, TGF Retinoic acid Hedgehog protein Wnt protein

HOMEODOMAIN PROTEINS
Transcription factor family with Helix turn-Helix motif. They contain highly conserved 60 amino acid sequence(homeo domain) which can bind to target genes Genes encoding these proteins are called as Homeobox genes. These genes which has a small (180bp) conserved region of DNA first identified in homeotic genes of drosophilla Hox genes are mammalian homeobox genes which resemble homeotic genes.In mammals there are 39 hox genes and many non hox homeobox genes identified

Genes expressed during tooth development

Barx Bmp Dlx Fgf Gli Hgf Lef Lhx Msx Otlx Pax Pitx Ptc Shh Slit Smo Wnt RunX2 / Cbfa1 BarH1 homologue in vertebrates (TF) Bone morphogenetic proteins (SP) Distaless homologue in vertebrates (TF) Fibroblast growth factor (SP) Glioma-associated oncogene homologue (zinc finger protein)(TF) Hepatic growth factor (SP) Lymphoid enhancer-binding factor 1 (TF) Lim-homeobox domain gene (TF) Msh-like genes in vertebrates (TF) Otx-related homeobox gene (TF) Paired box homeotic gene (TF) Transcription factor named for its expression in the pituitary gland Patched cell-surface receptor for sonic hedgehog (SHH) Sonic hedgehog (SP) Homologous to Drosophila slit protein (SP) Smoothed PTC coreceptor for SHH Wingless homologue in vertebrate (SP) Runt-related transcription factor-2 Core binding factor alpha 1

BRANCHIAL HOX CODE

ODONTOGENIC HOMEOBOX CODE

EPITHELIAL MESENCHYMAL INTERACTION AT VARIOUS STAGES

MOLECULAR FACTORS INVOLVED IN PERIODONTAL DEVELOPMENT

TRANSCRIPTION FACTORS(Genes involved)

Homeobox genes Msx1, Msx2, Dlx1, Dlx2, Dlx3, Otlx2,Barx1 Pax genes Pax9, Pax6 Lef1, Gli2/Gli3,Shh,Nfi-c
GROWTH FACTORS & MORPHOGENS

TGF 1 & 2, BMP2, 3, 4, &7, Activin, FGF 4,8 & 9, Hepatocyte growth factor, IGF1,PDGF

ROOT & PERIODONTIUM BEGINS TO DEVELOP AFTER HERS FORMATION

DEVELOPMENT OF CEMENTUM
Cells involved

Signaling molecules

Matrix synthesis

Mineralization

CELLS INVOLVED
Dental follicle proper

Ectomesenchyme-Neural crest derivative

Hertwigs Epithelial Root Sheath

OEE and IEE-Oral epithelium-Ectoderm of first arch derivative

DENTAL FOLLICLE(DENTAL SAC)

Three layers

1. Inner layer Dental follicle proper Vascular Fibro cellular condensation 2.Outer layer Vascular mesenchyme lining the alveolus 3.Midle layer Relatively avascular loose connective tissue 2nd and 3rd -Perifollicular mesenchyme Inner layer or all the layers are responsible for periodontal development ?

 Dental follicle has two differentiation compartments

1.Alveolar clade (produces osteoblast and fibroblast) 2.Cement clade (produces cementoblast and fibroblast)

AEFC Cementoblasts
Morophology Similar to periodontal ligament fibroblast (gene expression is different)

CIFC Cementoblasts
Cuboidal Similar to osteoblast

Rate of Matrix production

Slow and constant rate

More rapid than AEFC , not constant

Mode of Matrix production Cementoid Response to regulatory factors Regulatory factor for differentiation Precursor cells

Unipolar

Multipolar

Not present Mild

Present Respond well PTH signaling pathway, growth harmone Run X2 / Cbfa1

Run X2 / Cbfa1

Dental follicle / HERS Periodontal ligament stem cell/ERM - Odontogenic origin

Same May also have non odontogenic origin with alveolar bone or other extra ligamentary tissues

AEFC Cementoblasts
Matrix production Type I, Type III, V, VI,XII Major proteins BSP and OPN Non collagenous proteins

CIFC Cementoblasts

Collagen

Same Major proteins BSP and OPN more than AEFC

DSP and Osteocalcin are not produced

Produced

Cementum Attachment protein is produced

Produced

Proteoglycans - lumican, fibromodulin, versican, decorin not present

Present

Growth factors

EMP present
Cementum derived growth factor present

Not present
Present

SIGNALING MOLECULES INVOLVED IN CEMENTOGENESIS BMP BMP-2, BMP-4 & BMP-7 known to promote differentiation of putative cementoblast precursor cells.
PDGF, IGF - Promote cementum formation by altering cell cycle activities FGF - Promoting cell proliferation, migration and vasculogenesis. Epithelial factors - Enamel proteins, parathyroid hormone related protein & basement membrane constituents may play a role in cementogenesis.

(Cntd)
Major matrix proteins with cell adhesion motifs - Bone sialoprotein and osteopontin - Contain the cell adhesion motif arginine glycine aspartic acid (RGD sequence) - promoting adhesion of selected cells to the newly formed root surface. - Bone sialoprotein promotes mineral formation - Osteopontin regulates mineral growth Gla protein - Contain carboxy glutamic acid, calcium binding amino acid that may facilitate interaction with hydroxy apatite. Bone Gla protein (osteocalcin) regulate extent of mineralisation

Collagens - Type I collagen is the predominent collagen and it accommodates mineral deposition Type III & Type XII collagen is also found in small amount Transcription factors Runx-2 (runt related transcription factor 2) also known as cbfa 1 (core binding factor alpha 1) is likely to be involved in the differentiation of cementoblast. BMPs promote expression of Runx2 Other factors Alkaline phosphatase - in mineralization Proteoglycan accumulate at the dentin cementum junction with other protein such as bone sialoprotein and osteopontin initiate mineralization and fiber attachment .

Cementum Attachment Protein (CAP) It is a 56 or 65 kDa collagenous protein which is different from other collagen types and adhesion molecules.
It regulates differentiation of cementoblast lineage by inducing and

enhancing the differentiation of putative cementoblastic progenitors and has the capacity to recruit fibroblastic progenitors to cementoblastic lineage. Cementum derived growth factor It is a IGF like molecule
It is the growth factor specific to cementum present in the extra

cellular matrix.
It is mitogenic to gingival fibroblast and alveolar bone cells.

SIGNALING MOLECULES & PATHWAYS

MATRIX SYNTHESIS-MAJOR EVENTS

Migration Attachment Proliferation Differentiation Matrix synthesis

MIGRATION
Migration of dental follicular cells to newly formed

pre dentin Migration of HERS cells Important proteins are fibronectin-a mesenchymal chemoattractant laminin- epithelial chemo attractant

ATTACHMENT
Important factors
fibronectin integrins

syndecan-proteoglycan
tenascin BSP

OPN
CAP

PROLIFERATION
Factors involved
IGF-1 GH TGF- FGF

DIFFERENTIATION
Factors involved BMP-2,4,7 Epithelial proteins-amelogenins Transcription factors-Runx-2(runt related transcription factor also known as cbfa1)

Matrix synthesis
After the initial root predentine formation and

detachment and disintegration of HERS

Formation of fringe fibers by follicular fibroblast

AEFC FORMATION
Predentine formation
Fragmentation of HERS Inductive signal from predentine and enamel proteins to DF

matrix synthesis by AEFC forming cementoblast

Inter digitations of fringe fiber and dentinal collagen fiber

Fringe fiber formation-DF fibroblast

Fringe fiber get connected to developing Pdl fiber

AEFC formation continues at the rate of 57micron/day

After mineralization of mantle dentine cementum mineralization procedes

CMFC,CIFC,AIFC FORMATION
Root formation reaches 2/3rd tooth enter functional stage
CIFC forming cementoblast extend cell process and deposit collagen matrix-multi polar way and faster rate

Cementoblst get entrapped as cementocytes

Sometime matrix formation become slow and unipolar resulting in AIFC formation

Haphazardly arranged collagen fiber in CIFC get arranged parallel to root surface

Collagen fiber get connected to dentinal collagen

During the formation of CIFC and AIFC some cementum get formed around developing Pdl

This results in the formation of CMFC

After mineralization of mantle dentine cementum mineralization procedes

ACELLULAR AFIBRILLAR CEMENTUM FORMATION

- Believed to be development anomaly - Focal disruption of reduced enamel epithelium - Contact of follicular cells to enamel - Differentiation of cementoblast - Consist of glycosaminoglycans and non fibrillar collagenous component (does not have 64 nm periodicity).

INTERMEDIATE CEMENTUM
- This (10n) noncellular amorphous layer near the cemento dential -

junction Secreted by inner layer of HERS before it disintegrates. Main function is to seal the dential tubules Composed of enamelin protein More calcified than the adjacent cementum or dentin. It is usually not seen in human teeth.

MINERALIZATION OF CEMENTUM
Ca10(PO4)6(OH)2 Structure - Crystal interior - Crystal surface - Hydration shell This allows exchange of ions Role of formative cell in mineralization - Create a micro environment that facilitate mineral ion handling - Secrete protein that stabilize Ca, Phosphate ions in body fluids and/or control their deposition Secretary calcium binding phosphoprotein gene cluster.
Hydroxyapatite

MECHANISMS OF MINERALIZATION
a.

Homogenous nucleation Hetrogenous nucleation

Booster theory Matrix vesicle theory

b.

Small membrane bound structure that buds off from the formative cells. Contain alkaline phosphatase, calcium adenotriphosphatase MMPs, Proteoglycans, anionic phospholipids which can bind Ca and inorganic phosphates . These are unique to mineralizing situation. Heterogeneous nucleation by other seeding agents

Deposition of apatite crystal is catalysed by specific atomic groups associated with surface holes, and pores of collagen fibrils. Non collagenous proteins regulate this process.
influenced by non collagenous proteins which can bind selectively to different surfaces of the crystal preventing further growth. blocks the crystal growth - Provide phosphate ions at mineralization site.

Crystal growth

Pyrophosphate

Alkaline phosphatase hydrolizes organic phosphate ions at an alkaline pH

DEVELOPMENT OF PDL

CELLS INVOLVED

SIGNALLING MOLECULES INVOLVED

MATRIX SYNTHESIS

ORGANISATION OF FIBER GROUPS

CELLS INVOLVED

FIBROBLAST
Alveolar clade and cement clade of dental follicle Ectomesen chymal origin Peri vascular connective tissue Dental papillawhich migrate to dental follicle during early development HERS may also be a source for pdl fibroblast

CELLS FOR NEURO VASCULAR DEVELOPMENT

Vascular -Mesodermal origin Neural - Ectodermal (neuroectodermal) origin

STEM CELLS PROGENITAR CELLS

Dental follicle HERS Perivascular cells

EVIDENCES FOR HYPOTHESIZING HERS CAN ALSO BE A SOURCE FOR PDL FIBROBLAST
Pdl fibroblasts express cytokeratin 19 Presence of simplified desmosomes and

desmosomal proteins between Pdl fibroblast

PDL FIBROBLAST- UNIQUENESS

Ectomesenchymal Origin

Prolifer High rate of proliferation than gingival fibroblast -ation Express greater alkaline phosphatase activity Greater CAMP activity than gingival fibroblast

Chemical profile

Cytoskel oton

Well developed cytoskeloton

SIGNALING MOLECULES

Transcription factors Homeobox genes Msx1, Msx2, Dlx1, Dlx2, Dlx3, Otlx2,Barx1 Pax genes Pax9, Pax6 Lef1, Gli2/Gli3,Shh,Nfi-c Growth factors TGF1 & 2, BMP2, 3, 4, &7, Activin, FGF 4,8 & 9, Hepatocyte growth factor, IGF1

MATRIX SYNTHESIS
Preemergence phase Emergence into the oral cavity

Full occlusal function

First occlusal contact

PRINCIPLE FIBERS--STAGES OF DEVELOPMENT

A-Pre-emergence
C-First occlusal contact

B-Emergennce
D-Full occlusal function

DIFFERENCE BETWEEN PRIMARY AND SUCCEDANEOUS TEETH

SUMMARY OF PRINCIPLE PDL FIBER DEVELOPMENT

fringe fibers, unorganised connective tissue matrix

Establishing continuity

Growth of collagen fibers

Intermediate plexus

PDL-DEVELOPMENT OF OTHER COMPONENTS

Development of oxytalan fiber

Only form of elastic fiber in Pdl .Usually form a three dimensional network around neuro vascular elements
Develoment of ground substance

Non collagenous glycoproteins and glycosaminoglycans Development of neurovascular elements

PERIODONTAL LIGAMENT AS A MESENCHYME

FETAL TISSUE High rate of turnover Collagen fibrils show unimodal size distribution (25-50nm) PDL Pdl collagen has high turnover rate Pdl collagen fibrils show unimodal distribution with diameter 40-50nm

Type collagen is significantly present Pdl contain around 20% type collagen
Volume of ground substance is large Presence of immature elastin fiber(oxytalan fiber) High cellularity Pdl also has more amount of ground substance Oxytalan fibers are present in Pdl Pdl shows high cellularity (fibroblast occupy 45% of the tissue)

What regulates the maintenance of Pdl as a non mineralized tissue between two mineralized tissues ?
Clearly defined domains in the Pdl space

Cementum related domain Pdl related domain Alveolar bone related domain Cell diversity and sub population in the Pdl Secretion of molecules which can regulate the extent of mineralisation Balance between BSP and osteopontin Osteopontin is more in Pdl matrix Gla protein inhibit mineralisation Type XII collagen MSX2 - Suppress RunX2 transcriptional activity-Prevents ostogenic differentiation

ROLE OF PERIODONTAL LIGAMENT STEM CELLS

DEVELOPMENT OF ALVEOLAR BONE

DEVELOPMENT OF JAWS
Maxilla and mandible develops from First

Branchial arch(mandibular arch).

Arch has ectoderm endoderm and mesoderm

As neural crest cell migrate into the arch most of

the mesenchymal tissue is replaced by ectomesenchyme and first arch develops into maxillary and mandibular prominence
This later develops into maxilla and mandible

DEVELOPMENT OF MANDIBLE
Meckles cartilage has only positional relationship

with developing mandible but makes no contribution to it Neural part of mandible develops by the intra membranous ossification of the condensed mesenchyme formed at the angle of division of inferior alveolar nerve into mental and incisive branches Alveolar part develops as bony septa and bridges seperaitng the individual tooth germs Mascular part develops with the development of muscular attachment Three secondary cartilages (condylar, coronoid, symphyseal) also assist in further growth

DEVELOPMENT OF MAXILLA
Develops by intramembranous ossification of the

mesenchyme of maxillary process of the 1st arch Center of ossification is closely associated with the cartilage of nasal capsule Primary ossification center is in the angle of division of infra orbital nerve into anterior superior alveolar nerve Alveolar part forms around developing tooth germs

DEVELOPMENT OF ALVEOLAR BONE

Cells involved Signaling molecules Matrix synthesis Mineralization

CELLS INVOLVED
Osteoblast

Dental follicle

Ectomesen -

chyme

(Neural crest origin)

Osteoblast Osteoclast

Mesodermal origin Hematopoietic origin

Determined OP cells-Present in bone marrow, endosteum ,periosteum OSTEO PROGENITAR CELLS

Inducible OP cells mesenchymal cells of other organs , pericytes

TYPES OF OSTEOGENIC CELLS

Pre osteoblast- Appears like an inactive fibroblast Osteoblast- Cuboidal to low columnar in shape

Abundent RER and golgibodies

Osteocytes- Stellate shape, Within the lacunae,Less

synthetic and secretary activity,participate in blood Ca homeostasis,sense mechanical loading

Bone lining cells- Elongated cells,No synthetic activity,

Act as gatekeepers, protecting the bone surface from osteoclasts, regulating the ionic composition of bone fluid, and regulating the initiation of new bone formation

SIGNALING MOLECULES

Master gene for osteoblast differentiation

Cbfa1 gene is the master gene for mesechymal cell

differentiation into osteogenic cell lines This gene is induced by BMP7

Transcription factors
Cbfa1 protein act as a transcription factor for osteocalsin, osteopontin, BSP, and collagen AP -1(Activating factor -1) produced by the association of protein encoded by C-fos and C-jun genes is another regulator of bone cell proliferation

OTHER SIGNALING MOLECULES

BMPs-

BMP2,3,4,6 and 7 have bone inductive activity . BMP 2 is chemoattractent to osteoblast. BMP 7 for proliferation and differentiation
bFGF- increases the proliferation and differentiation

of osteogenic cells
Colony stimulating factors- Granulocyte-Macrphage

CSF stimulate osteoblst, Monocyte CSF stimulate preosteoclast differentiation

SIGNALING MOLECULES(CONTD)
PDGF- Chemotactic and mitogenic factor for

osteoblastic cells IGF and TGF-- Stimulate osteoblast Vit D Glucocorticids Retinoic acid

SIGNALLING MOLECULES&SIGNALLING PATHWAYS

DEVELOPMENTAL SEQUENCE OF OSTEOBLAST (after differentiation)

1- Proliferative phase- Synthesis of matrix 2- Maturative phase- Making the matrix

competent for mineralization

3- Mineralisation phase

MATRIX SYNTHESIS
The developing tooth germs are encased in rudimentary alveolar processes in the maxilla and mandible (woven bone) which are formed by neural crest-derived ectomesenchyme

Alveolar bone proper is formed during root development and is derived from cells originating in the dental follicle

After the differentiation of follicle(alveolar clade) cells to osteoblast they secrete the bone specific extracellular matrix (osteoid)

COMPOSITION OF EXTRACELLULAR MATRIX

COLLAGEN
Type- 1 Type- 3

NONCOLLAGENOUS PROTEINS
Osteocalsin,Bone sialoprotein Osteopontin,Osteonectin, Fibronectin

GAGS & PROTEOGLYCA N

GAG-Decorin and Biglycan
ProteoglycanCondroitin sulphate, Heparin sulphate, Hyluronan, Dermatin sulphate

MINERALISATION
Homogenous nucleation

Booster mechanism Hetrogenous nucleation Seeding mechanismMatrix vesicles Collagen fibrils,Phosphoproteins

ROLE OF OSTEOBLAST IN MINERALIZATION

Production of primary vesicles- For the initiation

of mineralization
Secretion of enzymes- control the mineralization Regulate the number ions available for

mineralization

ALVEOLAR BONE REMODELLING

By osteoblst & osteoclast

Woven bone Coarser ,less mature, osteocytes are irregularly dispersed

Lamellar bone More regular fibrillar matrix and osteocytes with haversian system(osteons) which gives lamellar pattern

DIFFERENCE BETWEEN PRIMARY AND SUCCEDANEOUS TEETH

PRIMARY TEETH & PERMENENT MOLAR Alveolar bone formation starts along with the root formation and subsequent eruption of teeth

SUCCEDANEOUS TEETH Initially they occupy the same osseous cavity with their predecessor . As the predecessor erupts they occupy a separate cavity lingual and apical to the primary teeth. During eruption the roof of the bony cavity ,the root and alveolar housing of the primary teeth get resorbed and succedaneous teeth occupy the vacant area .Only after this alveolar bone deposition starts

DEVELOPMENT OF GINGIVA

COMPONENTS OF GINGIVA
Oral epithelium

Epithelium

Sulcular epithelium

Junctional epithelium

GINGIVA

Fibroblast Gingival fibers

Connective tissue

Non collagenous proteins

Neurovascular elements

DEVELOPMENT OF GINGIVAL EPITHELIUM- CELLS INVOLVED

Developed from oral mucosal epithelium Ectodermal origin Oral mucosal epithelium Ectodermal origin Reduced enamel epithelium-Enamel organ Ectodermal origin

Outer Oral epithelium

Sulcular epithelium

Junctional epithelium

DEVELOPMENT OF JUNCTIONAL EPITHELIUM

1. Formation of reduced enamel epithelium 2. Union of REE and Oral epithelium 3. As the tooth erupts REE is converted into JE Changes during conversion

Cuboidal cells derived from ameloblast begin to flatten and align parallel to tooth surface and take appearance of JE. Since these cells which have lost capacity to divide get exfoliated at base of sulcus and cells from stratum intermedium which has proliferative capacity get transformed into JE

PRIMARY EPITHELIAL ATTACHMENT Attachment of reduced enamel epithelium to enamel of unerupted crown

SECONDARY EPITHELIAL ATTACHMENT After the conversion of REE to JE the attachment is referred as secondary epithelial attachment

EPITHELIAL ATTACHMENT APPARATUS Mediated by hemidesmosomes of DAT (Directly Attached to Tooth) cells and internal basal lamina

Characteristics Origin Keratinization

Outer Oral epithelium Oral epithelium Parakeratinized Sometimes orthokeratinized Well stratified

Sulcular epithelium Junctional epithelium Oral epithelium Nonkeratinized Reduced enamel epithelium Nonkeratinized

Stratification

Stratified but granulosam and corneum are absent

Poorly stratified

Proliferation

Lesser proliferation among three Not permeable to water soluble substances Narrowest More than SE& JE

Higher than OEE but Higher proliferation lesser than JE Moderately permeable Narrower than JE More than JE Highly permeable

Permeability

Intercellular Space Desmosomes& tonofilaments

Widest among three Least among three

Retepegs

Present

Normally absent, appears in inflammation

Normally absent, appears in inflammation

DIFFERENT VIEWS ABOUT JE

JE is an incompletely developed stratified

squamous epithelium
JE can be viewed as a structure that evolves

along a different pathway and produces the components of epithelial attachment instead of progressing into keratinized epithelium This could be due to the functionally different connective tissue which support JE

DEVELOPMENT OF CONNECTIVE TISSUE

Dento gingival& transseptal- Dental follicle-Ecto mesenchyme- Neural crest derived Gingival Other fibers- Oral mucosal connective tissue- Mesodermal or Neuralcrestal

fibers
Peri follicular mesenchyme- Stomedial mesodermal or Neuralcrestal

Fibrobla st

Non collagenou s proteins

From fibroblast

Neuro Neuro ectoderm and mesoderm respectively vasculat ure

TYPES & FUNCTIONS OF GINGIVAL FIBERS

GINGIVAL FIBROBLASTSFEATURES
Functional subpopulations

Fibroblsts from marginal gingiva secrete more collagen and grondsubstance than attached gingiva when exposed to diphenylhydantoin. High active and low actie fibroblast which respond differently to drugs which causes enlargement Fibroblast from tip of connective tissue papilla retain fetal migratory phenotype and produce migration stimulatory factor whereas fibroblasts from deeper layers not.
Gingival fibroblasts do not come into contact with the

root during development like Pdl fibroblasts

VARIABILITY IN THE CONNECTIVE TISSUE COMPARTMENT

Connective tissue which support JE is

developmentally ,structurally and functionally different from connective tissue which support oral and sulcular epithelium Developmental difference dental follicular origin Structural difference Extensive vascular plexus and inflammatory cells Functional difference non permissive for epithelial growth and differentiation

COMPOSITION OF EXTRACELLULAR MATRIX OF GINGIVA

Collagen
Type 1&3laminapropria Type 4- basement membrane Type 5-Aroud blood vessels Type 6- Micro fibrils

Proteoglycans
Decorin Biglycan Versican Syndecan

GAGs
Hyaluronan Heparan sulphate Chondrotin sulphate Dermatan sulphate

Noncollagenous proteins Fibronectn, Osteonectin, Tenascin, Elastin

DEVELOPMENT OF PERIODONTAL VASCULATURE

1st aortic arch (mesodermal origin) is the artery of the 1st

branchial arch. This later undergoes partial regression and remnants become part of maxillary artery Vasculogenesis
Angioblastic cords Angiblastic plexus

Mesoderm

Angioblast

Clusters of blood vessls are formed around the tooh germ in the dentl follicle which eventualy form the vasculature of periodontium VEGF is the major growth factor involved

DEVELOPMENT OF PERIODONTAL INNERVATION

Trigeminal nerve is the nerve of 1st arch

Ectoderm

Neuro ectoderm

Neurons

Nerve fibers ramify and form arich plexus around the

tooth germ in the dental follicle. This later develops into the sensory supply of periodontium Nerve growth factors -- neurotrophins, semaphorin, and glial cell line derived growth factor Receptors Mechano receptors,nosiceptive receptors &sensory nerve endings

TO CONCLUDE
Human periodontium is a specialised type of thecodontal

tooth attachment 1st arch derived epithelium & Neural crest derived ectomesenchyme are the essential components needed for its development Epithelial mesenchymal interaction is the key event in the development Dental follicle proper is the major contributor for periodontal development along with HERS Periodontal development is entirely depends on tooth root develoment Homeobox genes, Cbfa 1, BMPs, and various other transcription factors and growth factors play important role in periodontal development

 Genetically and phenotypically different

subpopulations of fibroblasts and cementoblasts exist in the periodontium Periodontal ligament contains the precursor for all these cells. Whether different precursors exist or same precursor gives all types of cells is not clear The exact signaling molecules and the pathways directing these cells to a particular cell type is still not clear. Better understanding in these aspects will help in regenerative therapy

REFERENCES
Ten cates oral histology 7th edition - Antonio Nanci Orabans oral histology and embryology Edited by

S.N.Bhaskar Development function and evolution of teeth Mark F. Teaford Essentials of oral histology and embryology James K. Avery Biology of Periodontal tissues P.Mark Bartold, A. Sampath Narayanan Oral cells and tissues P.R.Garant Fundamentals of periodontics 2nd edition-T.J. Wilson, K.S.Kornman Clinical peridontology and Implant dentistry -5th edition- Jan Lindhe

REFERENCES
Periodontol 2000;2006(40):11-28

Periodontol 2000;2006(41):196-217
Periodontol2000;2000 (24) Periodontol 2000;1999(19):8-20

Periodontol2000;1997(13)
J Dent Res 2005, 84(5):390-406 J Dent Res 2007, 86(7):594-599

J Periodont Res 2009;44:199-210

J Periodont Res 2009;44:81-87