1. Development of Periodontium
(a largely ecto-mesenchymally derived unit )

2. Contents : Introduction Development of teeth Stages of tooth growth
Hertwig’s epithelial root sheath & root formation
Development of cementum/ cementogenesis
Development of PDL
Development of alveolar bone
Development of dentogingival unit
conclusion

3. Introduction
The periodontium is simply defined as the tissues supporting and investing the tooth - consists of cementum, PDL, bone lining the alveolus & that part of the gingiva facing the tooth.
The tissues supporting the tooth are developmentally derived from the dental follicle proper, whereas those investing the tooth, that is the gingiva, are an adaptation of the oral mucosa.
- Richard Ten Cate

4. The widespread occurrence of periodontal diseases & the realization that periodontal tissues lost to the disease can be repaired has resulted in considerable effort to understand the factors & cells regulating the formation, maintenance, & regeneration of the periodontium. - Ten Cate et al Periodontology 2000, Vol. 13

5. Reciprocal induction

6. Tooth germ
Ectodermal cells of dental lamina divide more rapidly & form little knobs that grow into underlying mesenchyme.
These little down growths from the dental lamina represents the beginning of enamel organ of the tooth bud.

7. As cell proliferation continues...
Each enamel organ increase in size & sink deeper into the ectomesenchyme, & due to differential growth shape also changes.
First it takes a shape that resembles a Cap, with an outer convex facing the oral cavity & inner concavity.

8. Three basic parts of Tooth germ
Enamel organ (ectodermal component)
Dental papiila
Dental sac or dental follicle
Ectomesenchymal component
Enamel organ
Enamel
Dental papilla
dentin
pulp
Dental follicle
Cementum
PDL
Alveolar bone

9. Hertwig’s epithelial root sheath (HERS) & root formation
Schour & Massler suggested that the major function of the Hertwig’s epithelial root sheath is to induce and regulate root formation, including the size, shape and number of roots
Characteristics of HERS:
HERS consists of inner & outer enamel epithelia only.
Cells of inner layer remain short in size and induce the differentiation of radicular dental papilla cells into odontoblast which lays down first layer of radicular dentin.

10. 3. Some outer layer cells in coronal root region induce cells of dental follicle to differentiate into cementoblasts similar to osteoblasts which give rise to acellular cementum. 4. Slavkin suggests, since the epithelial cells of the inner layer of Hertwig’s epithelial root sheath are analogous to the preameloblasts, it is suggested that they might secrete enamel matrix proteins over the newly deposited root dentin. 5. In addition to these matrix proteins there are also the components of the epithelial basement membrane, such as laminin and collagen type IV are sectreted by root sheath.

11. Dental Cementum
The dynamic tissue
covering the root

12. Development of cementum
Process of cementum development is called as “cementogenesis”.
Cementum is calcified, avascular mesenchymal tissue that forms outer coverings of the anatomic root.
It was first demonstrated microscopically in 1835 by two pupils of purkinje.
It is a specialized connective tissue that shares some physical, chemical & structural characteristics with compact bone.

13. Deposition of dentin along the inner aspect of HERS
Cementogenesis (Briefly)
Deposition of dentin along the inner aspect of HERS
Breaking up of HERS allowing the newly formed dentin to come in contact with cells of dental follicle
Differentiation of cementoblasts along the external surface of the root
Protein secretion by cementoblasts mainly collagen & proteoglycans which forms the organic matrix of cementum
Phase of matrix maturation, which subsequently mineralizes to form cementum

14. [Hertwig’s epithelial root sheath is broken up & separated from root, and differentiation of cementoblasts lead to formation of cementum]

15. Varieties of cementum
Two basic types of cementum, hence they are usually classified on the basis of presence of cementocyte (cellular cementum) or absence of it (acellular cementum).
It can also be classified on the basis of the types of fibers (extrinsic/intrinsic) presence or their absence (afibrillar cementum).
acellular extrinsic fiber cementum is regarded as Primary cementum as it forms first.
Cellular cementum is regarded as secondary cementum because it forms later than primary cementum.

16. Growth factor families involved in the differentiation of cemetoblasts from dental follicle
TGFβ 1-5
BMP2-8
EGF & IGF
PGE2 & PGF2α enhance differentiation by activating protein kinase cell signalling pathway
Fibroblast growth factor promotes proliferation, migration & angiogenesis
CAP, BSP and osteopontine helps in attachment of differentiated cells to newly forming tissue

17. Development of acellular cementum
Development of acellular cementum is associated with secretion of enamel matrix protein (EMP) by HERS after mineralization of first layer of dentin adjacent to the root.
Enamel proteins including amelogenin & certain basement membrane constituents are reported to be involved in epithelial-mesenchymal reaction.
HERS also secrete cementum related proteins like Bone sialoprotein (BSP), osteopontin & fibrillar collagen.

18. At the same time fibroblast precursors cells from dental follicle come in contact with predentine matrix and start depositing bundle of collagen fibrils to form a thin layer of perpendicularly oriented “Sharpey’s fibers” or “fringe fibers”.
Sharpey’s fibers interdigitate with unmineralized dentin at one end and into extracellular compartment of acellular cementum at another end.
As the mineralization front advances, it contacts the sharpey’s fibers and they undergo slow mineralization to complete the process of acellular extrinsic fiber cementum formation.

19. Development of cellular cementum
(a more rapidly formed & less mineralized variety of cementum)
Formation occurs after at least half the root is formed.
Development can be divided into 2 stages:
An early stage in which extrinsic sharpey’s fibers produced by fibroblasts are few & traces of intrinsic fibers produced by cementoblasts are randomly arranged
Later stage of cementogenesis- it closely resembles bone formation. Cementoblasts and cementocytes are involved in the secretion of intrinsic fibers.

20. Rapid and multipolar mode of mineralization takes place
Entrapped cementoblasts are called as – cementocytes
Cementcytes have processes that lodge in canaliculi that communicate but do not form a syncitium that extends all the way to the surface, as is the case with in the bone.

21. Cementoid tissue & calcification of matrix
The uncalcified matrix is called as cementoid.
the growth of cellular cementum is a rhythmic process, and as a new layer of cementoid is formed, the old calcifies.
Gla proteins – osteocalcin & osteonectin acts as neucleators for mineralization due to their strong affinity for calcium & BSP.
Alkaline phosphatase promotes mineralization.
Osteopontine regulates growth of apatite crystals.
Major proteoglycan located in non-mineralized cementum is keratan sulfates- lumican & fibromodulin.

22. “Periodontal ligament” Soft-tissue continuity Between the mineralized
Tissues of periodontium

23. The periodontal ligamment (PDL) is composed of a complex vascular & highly cellular connective tissue that surrounds the tooth root & connects it to the inner wall of the alveolar bone.
Over the years it has been described by number of terms:
Desmodont
Gomphosis
Pericementum
Dental periosteum
Alveodental ligament
Periodontal membrane

24. Development
Development of PDL begins with root formation, prior to tooth eruption.
The dental follicle cells located between the alveolar bone & HERS are composed of two subpopulations:
Mesenchymal cells of dental follicle proper
Perifollicular mesenchyme
Perifollicular mesenchymal cells bounded by mesenchymal cells of dental follicle proper.

25. As the root formation continues, cells in the perifollicular region and follicle proper are gain their polarity & the cellular volume & synthetic activity increases.
These cells obtain long & thin, elongated cytoplasm with increased amount of mitochondria, RER & active Golgi complex.
As a result, these cells actively synthesize & deposits collagen fibrils & glycoprotein in the developing periodontal ligament.
progenitors for periodontal ligament, osteoblast and cementoblast cells adopt a paravascular location in the periodontal ligament, and these cells, which exhibit some features of stem cells, can regenerate functional tissues when the need arises.

26. Developmet of principal fibers
Immediately before tooth eruption & for sometimes there after, active fibroblasts adjacent to the cementum of the coronal 1/3 of the root, aligne in oblique direction to the long axis of the tooth.
Soon, thereafter, first collagen fiber bundles of the ligament become discernible. These are the precursors of the alveolar crest fiber bundle group.
Later, similar fibers are observed on the adjacent osseous surface of the developing alveolar bone.

27. Both set of fibers, alveolar & cemental, continue to elongate toward each other, ultimately to meet, intertwine & fuse, & cross linking of individual collagen molecules occur.
By the time of first occlusal contact of the tooth with its antagonist, the principle fibers around the coronal 1/3 of the root, the horizontal group are almost completely developed
Oblique fibers in middle third of the root are still being formed.
After complete root apex is formed, apical group of fibers are developed.

28. (Inhibitors of mineralization)
PDL homeostasis
A remarkable capacity of PDL is that it maintains its width more or less, despite the fact, it is squeezed in between two hard tissues.
Various molecules have been proposed, which play a role in maintaining an unmineralized PDL.
Msx2
Bone sialoprotein
Matrix Gla proteins
(Inhibitors of mineralization)
Inhibit mineralized bone tissue
Prevents osteogening differentiation of PDL fibroblasts by repressing cbfa1 activity
osteopontin
Prostaglandins

29. Cell biology of normal PDL
Synthetic cells
Fibroblasts
Osteoblasts
cementoblasts
Resorportive cells
Osteoclasts
cementoclasts
Progenitor cells
Undifferentiated stem cells
Epithelial cells
Epithelial cell rests of malassez
Defense cells
Mast cells
Macrophages
eiosinophils

30. Epithelial cell rests of malassez
Roles attributed to the Epithelial Rest of Malassez cells range from bad to good.
Bad Role
Malassez cells are held responsible for the formation of periodontal cysts and tumours as a result of peri-apical inflammation associated with pulpal necrosis.
Epithelial Rest of Malassez cells contribute to the formation of the periodontal pocket because of their continuum with the junctional epithelium.
-Ohshima M, Nishiyama T, Tokunaga K, Sato S, Maeno M, Otsuka K.

31. Good Role
The cells of the Epithelial Rest of Malassez may protect the root from resorption
- Wallace JA, Vergona K.
Epithelial cells Rest of Malassez secrete hyaluronic acid, which contributes to the formation of the loose connective tissue characteristics of the periodontal ligament & react to mechanical stress, like that associated with orthodontic tooth movement, by increasing their proliferation rate and cell size Brunette DM & Merrilees MJ, Sodek J, Aubin JE
Epithelial Rest of Malassez - help in cementum repair because of their ability to activate matrix proteins, such as amelogenin, which are also expressed during tooth development - Hamamoto Y, Nakajima T, Ozawa H, Uchida T.

32. ( The socket that is never stable)
Alveolar Bone
( The socket that is never stable)

33. The alveolar process is the portion of the maxilla & mandible that forms & supports the tooth sockets.
It forms when the tooth erupts to provide the osseous attachment to the forming PDL & it disappears gradually after the tooth is lost.

34. Intramembranous ossification
Bone formation
Intramembranous ossification
Formation of bone matrix
Formation of woven bone
Appositional growth & formation of harvesian system (osteon)
Endochondral bone formation
Formation of cartiagenous model

35. Development of alveolar process
An alveolar bone in the strict sense of words develops only during the eruption of the teeth.
As the root & its covering of primary cementum form, new bone is deposited against the crypt wall.

36. Crystal form coalescing bone nodules with fast growing, non oriented collagen fibers- is the substructure of woven bone, first bone formed in the alveolus.
Later, through bone deposition, remodelling & secretion of oriented collagen fibers in sheets, mature lamellar bone is formed.
Subsequently, a tissue may develop at alveolar crest that combines characteristics of cartilage & bone.
It is called as chondroid bone.

37. Structure of alveolar bone
Alveolar bone proper
(a thin lamella of the bone that surrounds the rootof the tooth & gives attachment to the principle fibers of the PDL)
Inner socket wall of thin compact bone
Bundle bone
Cribriform plate
Lamina Dura (radiographically)
supporting alveolar bone
(the bone that surrounds the alveolar bone proper
& gives support to the socket)
External plate of cortical bone
Spongy bone/ cancellous trabeculae

38. Bone remodeling
Bone is a highly dynamic connective tissue with continuous remodeling.
Process of bone formation & bone breakdown go on simultaneously, thus the bone represents the net results of a balance between the two processes
This phenomena is called as coupling of bone resorption & bone formation.
The main function of the remodeling are to prevent the accumulation of damaged & fatigued bone by regenerating new bone & to facilitate mineral homeostasis.

39. Mediators of bone remodeling
Mechanical factors : when stress is applied on the alveolar bone, two sites are formed, bone is resorbed at compression site & bone is deposited at tension site.
Parathyroid hormone
Vita. D metabolites
Growth factors
Bacterial products

40. Markers of bone turnover
Alkaline phosphatase
osteocalcin
Procollagen I extension peptide
Markers of bone formation
(serum markers)
Urine calcium
Urine hydroxyproline
Collagen crosslink fragments
Urine N-telopeptides
Urine C-telopeptides
Urine pyridinoline
Urine free deoxypyridinoline
Markers of bone resorption
(urinary markers)

41. Gingiva
The First
Responder

42. Gingiva is an adaptation of oral epithelium in areas involved in mastication of food
The gingiva is a part of the oral mucosa that covers the alveolar processes of the jaws & surrounds the neck of the teeth.- McCall

43. Clinical features of gingiva

44. Dentogingival junction (junctional epithelium)
The epithelium of the gingiva which gets attached to the tooth is called as junctional or attachment epithelium.
It consists of collar like band of stratified squamous non keratinizing epithelium, located at CEJ in healthy tissue

45. JE resembles reduced enamel epithelium (RER) in its structure in that they have a basal layer & few layers of flattened cells & express CK 5, 14, 19, which is typical of nondifferentiating tissue like RER.
Highest turnover rate of 5-6 days
JE is highly permeable & it has large intracellular spaces, so that neutrophils can easily pass in & out of the epithelium.
Permits easy flow of GCF

46. Development of dentoginval junction & gingival sulcus
After enamel formation is complete, the enamel is covered with REE, which is attached to the tooth by a basal lamina & hemidesmosomes
When tooth penetrates oral mucosa, the REE unites with oral mucosa and transformed into JE
JE proceeds in an apical direction, forming a shallow groove, the gingival sulcus between circumference of tooth & gingiva that encircles the newly erupted tip of the crown
Gingival sulcus deepens as a result of separation of the REE from actively erupting tooth & JE attains its position at CEJ of fully erupted tooth

47. Formation of JE & Gingival sulcus

48. Shift of dentogingival junction
The actual movement of crown towards the occlusal plane is called as a active eruption
The separation of primary attachment epithelium from the enamel is termed as passive eruption
crown exposure involving passive eruption & further recession has been described in four stages
firsr two stages may be physiologic but last two are probably pathologic.

49. Shift of dentogingival junction
Stage 1 stage 2 stage 3 stage 4
Shift of dentogingival junction

51. Reciprocal induction between oral ectoderm & mesenchymal cells derived from neural crest cells form the major pathway for the development of periodontal tissues.
Various histochemical molecules favours the differentiation of fibroblasts, cementoblasts & osteoblasts from the inner cells of the dental sac, which are also secreted at the time of periodontal regeneration or repair by PDL
PDL contains both formative & resorptive cells for cementum, A.bone & PDL itself.

52. Based on the information presented, it appears that the developed or adult periodontium retains its potential for repair/regeneration in the form of cells of the Epithelial Rest of Malassez, progenitor cells and stem cells, which can be induced to differentiate into cementoblast, osteoblast or periodontal ligament cells to regenerate periodontal tissues.

53. References: Textbook of Orban’s Oral histology & Embryology, 12th Ed.
Textbook of TenCate’s Oral histolgy & Embryology, 8th Ed.
Margarita zeichner-david, Regeneration of periodontal tissues: cementogenesis revisited, Periodontology 2000, Vol. 41, 2006, 196–217.
A. Richard ten cate, The development of the periodontium - a largely ectomesenchymally derived unit, Periodontology 2000, Vol. 13, 1997, 9-19.
Thomas HF, Kollar EJ. Differentiation of odontoblasts in grafted recombinants of murine epithelial root sheath and dental mesenchyme. Arch Oral Biol 1989; 34:
Textbook of clinical periodontology, F.A.Carranza, 10th Ed.