JUNCTIONAL EPITHELIUM

Junctional epithelium is a part of the gingival epithelium , that attaches the gingiva to the tooth. Hope this presentation helps you.

1. JUNCTIONAL EPITHELIUM HARIPRIYA RAJARAM DEPT OF PERIODONTICS PANINEEYA DENTAL COLLEGE HYDERABAD

2. CONTENTS INTRODUCTION HISTORICAL ASPECT DEVELOPMENT ANATOMICAL FEATURES MICROSCPOIC FEATURES DIFFERENCES BETWEEN DIFFERENT EPITHELIUM MOLECULAR ASPECTS OF JUNCTIONAL EPITHELIUM FUNCTIONS JUNCTIONAL EPITHELIUM IN POCKET FORMATION REGENERATION OF JUNCTIONAL EPITHELIUM JUNCTIONAL EPITHELIUM AROUND IMPLANTS CONCLUSION

3. INTRODUCTION ORAL MUCOSA CONSISTS OF Masticatory mucosa Specialized mucosa Oral mucous membrane lining the remained of the oral cavity

4. The gingiva is composed of gingival epithelium and gingival connective tissue. Furthermore, the gingival epithelium is in turn classified into the oral epithelium : covers the crest and outer surface of marginal gingiva and attached gingiva sulcular epithelium : lines the gingival Sulcus. junctional epithelium: which provides the contact between the gingiva and the tooth.

5. Historical aspect Gottlieb (1921) had reported that the " epithelial attachment " is organically united to the tooth surface.

6. Waerhaug (1952) concluded that the " epithelial attachment " belongs to the lining of the " physiological pocket ", that its cells adhere only weakly to the tooth surface, and that the bottom of that pocket is to be found at the cemento -enamel junction

7. Waerhaug’s concept (1960) He presented the concept of epithelial cuff . This concept was based on insertion of thin blades between the surface of tooth and the gingiva. Blades could be easily passed apically to the connective tissue attachment at CEJ without resistance. It was concluded that gingival tissue and tooth are closely adapted but not organically united.

8. Schroeder and Listgarten concept (1971) Primary epithelial attachment refers to the epithelial attachment lamina released by the REE. It lies in direct contact with enamel and epithelial cells attached to it by hemi-desmosomes. When REE cells transform into JE cells the primary epithelial attachment becomes secondary epithelial attachment . It is made of epithelial attachment between basal lamina and hemi-desmosomes

9. SCHROEDER AND LISTGARTEN (1977) Clarified the anatomy and histology of dentogingival junction in their monograph Fine structure of developing epithelial attachment of human teeth . MAX LISTGARTEN

10. definition Junctional epithelium is the non keratinized stratified squamous epithelium which attaches and form a collar around the cervical portion of the tooth that follows CEJ. -Carranza A single or multiple layer of non­ keratinizing cells adhering to the tooth surface at the base of the gingival crevice. Formerly called epithelial attachment. - Glossary of periodontal terms- AAP 4 th edition

11. Development Fully developed enamel is surrounded by REE and basal lamina

12. As the erupting tooth approaches the oral epithelium, the cells of the outer layer of the reduced dental epithelium (RE), as well as the cells of the basal layer of the oral epithelium (OE), show increased mitotic activity and start to migrate into the underlying connective tissue..

13. When the tooth has penetrated into the oral cavity, the REE cells transform into flat cells forming junctional epithelium. The cervical region of the enamel, however, is still covered by ameloblasts (AB) and outer cells of the reduced dental epithelium.

14. During the later phases of tooth eruption, all cells of the reduced enamel epithelium are replaced by a junctional epithelium (JE). This epithelium is continuous with the oral epithelium and provides the attachment between the tooth and the gingiva .

15. Anatomical features Junctional epithelium consists of a collar like band of stratified squamous non keratinizing epithelium. It is 3-4 layers thick in early life but, but the number increases with age to 10 or even 20 layers. It tapers from coronal end to its apical end, which is located at the CEJ in the healthy tissue. Periodontal ligament limits its apical e xtent, and coronally it is continuous with sulcular epithelium The length of junctional epithelium ranges from 0.25 to 1.35 mm

16. DENTOGINGIVAL UNIT The attachment of the junctional epithelium to the tooth is reinforced by the gingival fibers, which brace the marginal gingiva against the tooth surface. For this reason, the junctional epithelium and the gingival fibers are considered together as a functional unit referred to as the dentogingival unit .

17. Microscopic features Non-keratinizing stratified squamous epithelium is made up of two strata: basal layer and the supra-basal layer Basal layer – consisting of cuboidal cells, are arranged along the connective tissue interface Supra-basal layer – multiple layers of flattened cells lying parallel to tooth surface

18. Junctional epithelium is attached to 1.gingival connective tissue - external basal lamina 2. tooth surface - internal basal lamina.

19. External basal lamina contains the structures similar to that of typical basement membrane, with the lamina densa supporting the underlying connective tissue and lamina lucida lying in between the lamina densa and the basal cells . Internal basal lamina lacks true basement membrane components like: collagen IV and VII, laminin 1 while it contains laminin 5 and type VIII collagen (usually absent in typical basement membrane); hence it is considered as a specialized extracellular matrix.

20. The single layer of cell, lying in contact with tooth surface, is referred to as DAT ( Directly attached to tooth ) cells Salonen JI in the year 1994 proved the proliferative potential of these cells in his study. The existence of a proliferating population of epithelial cells (DAT cells) in a supra-basal location, several layers away from the connective tissue, is a unique feature of the junctional epithelium.

21. ZONES OF JUNCTIONAL EPITHELIUM Apical – germination Middle – adhesion Coronal – permeable

22. FEATURES OF JUNCTIONAL EPITHELIAL CELLS: These cells contain dense cytoplasm abundant amount of rough endoplasmic reticulum, Golgi complex (LARGE) lysosomal bodies polyribosomes . few tonofilaments Absenc e of Keratinosomes (ODLAND BODIES) Acid phosphatase

23. Cytokeratins (CK) are the intermediate filament proteins of cytoskeletal family and form the main structural proteins of these Junctional epithelial cells . They express CK5,CK10, CK13, CK 14, CK16 and CK19 . The expression of CK19 being high, found in almost all the layers of junctional epithelium, have been regarded as the characteristic histological marker for Junctional epithelium .

24. The cells exhibit relatively loose intercellular junctions comprising of few desmosomes, adherens junctions and occasional gap junctions . The fluid-filled inter-cellular spaces are responsible for remarkable permeability . Intercellular spaces are occupied by mononuclear leukocytes of varied nature. Different types of cells like the polymorpho nuclear leukocytes, lymphocytes, macrophages, antigen-presenting cells, Langerhans cells are seen to exist in and around the junctional epithelium cells It is also being innervated by sensory nerve fibers .

25. Characteristics Outer Oral epithelium Sulcular epithelium Junctional epithelium Origin Oral epithelium Oral epithelium Reduced enamel epithelium Keratinization Parakeratinized Sometimes or t h okera t i n i zed Nonkeratinized Nonkeratinized Stratification Well stratified Stratified but granulosam and corneum are absent Poorly stratified Proliferation Lesser proliferation among three Higher than OEE but lesser than JE Higher proliferation Permeability Not permeable to water soluble substances M o de r a t e l y permeable Highly permeable Intercellular Space Desmosomes& tonofilaments Narrowest More than SE& JE Narrower than JE More than JE Widest among three Least among three Retepegs Present Normally absent, appears in inflammation Normally absent, appears in inflammation DIFFERENCES BETWEEN THE EPITHELIUM

26. EPITHELIAL ATTACHMENT APPARATUS The gingiva (specifically junctional epithelium) is adherent to tooth through a structural complex, referred to as epithelial attachment apparatus This consists of [1]hemidesmosomes [2] a basal lamina, i.e. internal basal lamina, to which the cells are attached through hemidesmosomes

27. HEMIDESMOSOMES Hemidesmosomes have a decisive role in the firm attachment of the cells to the internal basal lamina on the tooth surface The hemidesmosome comprises of an attachment plaque, cytokeratin filaments and a sub-basal lamina dense plate The interaction between IBL and cell surface macro-molecule helps in cell motility, adhesion, synthetic capacity, tissue stability, regeneration and response to external signal

28. MOLECULAR ASPECT OF JUNCTIONAL EPITHELIUM CELL ADHESION MOLECULES MOLECULAR FACTOR FUNCTION INTEGRINS MEDIATE CELL MATRIX AND CELL-CELL INTERACTION EPITHELIAL CADHERIN intercellular adhesion structural integrity CEACAM1 ( carcino embryonic Ag- related cell adhesion molecule 1) Adhesion between epithelial cells; guidance of PMNs through the junctional epithelium; regulation of cell proliferation, stimulation, and co-regulation of activated T-cells; cell receptor for certain bacteria CAM-1 Mediates cell-cell interactions in inflammatory reactions; guiding PMNs toward the sulcus bottom

29. Interleukin-8 Chemotaxis; guiding PMNs toward the sulcus bottom Interleukin-1 Tumor necrosis factor Pro-inflammatory cytokines that contribute to the innate immune defense CYTOKINE GROWTH FACTORS AND CORRESPONDING RECEPTORS Epidermal growth factor (EGF) Mitogen that participates in epithelial growth, differentiation, and wound healing Epidermal growth factor receptor (EGFR) Signal transduction

30. PROTEASES Tissue plasminogen activator (t-PA) Serine protease that converts plasminogen into plasmin, which in turn degrades extracellular matrix proteins and activates matrix metalloproteinases MMP-7 OR MATRILYSIN Proteolytic degradation of the extracellular matrix NATURAL ANTIMICROBIAL PEPTIDES AND PROTEINS α - defensins PMN-produced antimicrobial substances that contribute to the innate immune defense Human -defensin Epithelially produced antimicrobial substances that contribute to innate host defense

31. FUNCTIONS Barrier : junctional epithelium forms a dynamic seal around the tooth, protecting delicate periodontal tissues from external environment, and acts as a physical barrier. Rapid turnover : junctional epithelium shows exceptionally high turnover rat e, which not only maintains a structural integrity but also adapts itself as per need. Anti-microbial function : junctional epithelium has no keratinized layer at its free surface, some special structural and functional characteristics compensate for absence of this barrier, thereby help to maintain a potent anti-microbial mechanism, which is a unique property of J.E

32. TURN OVER OF JUNCTIONAL EPITHELIAL CELLS The turnover rate of junctional epithelium is exceptionally rapid Previously it was thought that only epithelial cells facing the external basal lamina were rapidly dividing. However, recent evidence indicates that a significant number of the DAT cells are, like the basal cells along the connective tissue, capable of synthesizing DNA , which demonstrates their mitotic activity .

33. At the coronal part of the junctional epithelium, the DAT cells typically express a high density of transferrin receptors which supports the idea of their active metabolism and high turnover The existence of a dividing population of epithelial cells (DAT cells) in a suprabasal location, several layers from the connective tissue, is a unique feature of the junctional epithelium. The distinct phenotype may result from specific permissive or instructive signals provided by the internal basal lamina matrix on the tooth surface.

34. POSSIBLE PATHWAYS FOR TURN OVER OF DAT CELLS (1). The daughter cells produced by dividing DAT cells replace degenerating cells on the tooth surface (2) the daughter cells enter the exfoliation pathway and gradually migrate coronally between the basal cells and the DAT cells to eventually break off into the sulcus, or (3) epithelial cells move/migrate in the coronal direction along the tooth surface and are replaced by basal cells migrating round the apical termination of the junctional epithelium.

35. JUNCTIONAL EPITHELIUM IN THE ANTIMICROBIAL DEFENCE 1. In the coronal part , rapid cell exfoliation occurs due to high turn over rate and funneling of cells towards the sulcus prevents bacterial colonization . 2. Laterally , the (external) basal lamina forms an effective barrier against invading microbes . 3. Active antimicrobial substances are produced in junctional epithelial cells. These include defensins and lysosomal enzymes

36. Epithelial cells activated by microbial substances secrete chemokines, e.g. interleukin- 8 and cytokine s, e.g. interleukins -1 and -6, and tumour necrosis factor- that attract and activate professional defense cells, such as lymphocytes ( LC) and polymorpho- nuclear leukocytes (PMN).  

37. Recently, it has been found that the junctional epithelial cells lateral to DAT cells produce matrilysin (matrix metalloproteinase-7) . It has the following effects. this enzyme is able to activate the precursor peptide of - defensin , an important antimicrobial agent of mucosal epithelium . release of bioactive molecules from the cell surfaces which play a role in the inflammatory reaction  

38. because of rapid cell division and funnelling of junctional epithelial cells towards the sulcus hinder bacterial colonization. Laterally, the (external) basement mem- brane forms an effective barrier against invading microbes Active antimicrobial substances are produced in junctional epithelial cells. These include defensins and lysosomal enzymes

39. (5)Epithelial cells activated by microbial substances secrete chemokines, e.g. interleukin- 8 and cytokines, that attract and activate professional defense cells, such as lymphocytes (LC) and polymorpho- nuclear leukocytes (PMN). Their secreted product, in turn, cause further activation of the junctional epithelial cells .

40. The GCF passing through the junctional epithelium determines the environmental conditions and provides sufficient nutrients for the DAT cells to grow. The main route for GCF diffusion is through the (external) basement membrane and then through the relatively wide intercellular spaces of the variable thickness junctional epithelium into the sulcus. ROLE OF GCF

41. During inflammation the GCF flow increases and its composition starts to resemble that of an inflammatory exudate The increased GCF flow contributes to host defense by flushing bacterial colonies and their metabolites away from the sulcus, thus restricting their penetration into the tissue

42. JUNCTIONAL EPITHELIUM IN GINGIVITIS INITIAL LESION: increase in PMNs

43. EARLY LESION : 1.densely infiltrated with neutrophils 2.development of rete pegs or ridges

44. ESTABLISHED LESION : 1. Widened intercellular spaces that are filled with granular , cellular debris from disrupted neutrophils, lymphocytes and monocytes. 2. Rete pegs protrude into the connective tissue and basal lamina is destroyed in some areas.

45. ROLE OF JUNCTIONAL EPITHELIUM IN INITIATION OF POCKET FORMATION Conversion of junctional epithelium to pocket epithelium is regarded as a hallmark in the development of periodontitis the initiation of pocket formation may be attributed to the detachment of the DAT cells from the tooth surface or to the development of an intra-epithelial split

46. With increasing degrees of gingival inflammation, both the emigration of PMNs and the rate of gingival crevicular fluid passing through the intercellular spaces of the junctional epithelium increases causing focal disintegration. In contrast, the bacteria and their products also have the opportunity to enter the junctional epithelium .

47. Among the virulence factors produced by P. gingivalis , gingipains specifically degrade components of the epithelial cell-to-cell junctional complexes . The proteolytic disruption of the epithelial integrity may not only be a significant factor in the initiation of pocket formation, but may also pave the way for bacterial invasion into the sub- epithelial connective tissue in advanced stages of the lesion.

48. Apical shift of junctional epithelium : collagenase released by various cells such as fibroblasts, PMNs and macrophages degrade the collegen matrix. Apical cells of JE proliferate along the root surface and extend finger like projections that are 2-3 cell in thickness .

49. Coronal detatchment of junctional epithelium : As a result of inflammation , the PMNs invade the coronal end of junctional epithelium in increasing numbers. When the relative volume of PMNs reach 60% or more of junctional epithelium , the epithelium loses its cohesiveness and detatches from the tooth surface. apical shift of JE

50. CHANGES SEEN IN JUNCTIONAL EPITHELIUM IN PERIODONTAL POCKET: JE at the pocket is much shorter than JE at base of normal sulcus. Slight degenerating changes,

51. REGENERATION OF JUNCTIONAL EPITHELIUM Injury to junctional epithelium may occur due to: Accidental trauma Toothbrushing Flossing Eating Intentional Periodontal surger y

52. Following probing , a new and complete attachment indistinguishable from that in controls was established 5 days after complete separation of the junctional epithelium from the tooth surface ( Taylor and Campbell, 1972 ) Waerhaug (1981) studied healing of the junctional epithelium after the use of dental floss at premolars in 12-year-old humans. Then new attachment of junctional epithelial cells started 3 days after flossing ceased. Finally the cell populations on the experimental and control surfaces were again indistinguishable after two weeks In general, a new junctional epithelium after gingivectomy forms within 20 days

53. Long junctional epithelium If the epithelium proliferates along the root surface before other tissues, it results in the formation of long junctional epithelium. The long junctional epithelium consists of two or three layers aligned parallel to the tooth surface. This epithelium attaches to the cementum surface by hemidesmosomes and the basal lamina. The epithelium is permeable due to its wide intercellular spaces.

54. Fewer capillaries underneath the long junctional epithelium are evident than in the normal junctional epithelium Listgarten et al . suggested that the long junctional epithelium is a transient feature of the healing process on the road to connective tissue attachment, but it is not a final healing stage

55. BIOLOGIC WIDTH BIOLOGIC WIDTH is defined as the dimension of the soft tissue which is attached to the portion of the tooth coronal to the crest of the alveolar bone. It is important from the restorative point of view because its violation leads to complications like gingival enlargement alveolar bone loss and improper fit of the restoration.

56. The average histological width of connective tissue attachment was 1.07mm. The mean average length of epithelial attachment was 0.97mm with the range of 0.71mm-1.35mm. The average combined histological width of connective tissue attachment and junctional epithelium was 2.04mm , which is referred to as the BIOLOGIC WIDTH

57. JUNCTIONAL EPITHELIUM AROUND IMPLANTS The junctional epithelium around implants always originates from epithelial cells of the oral mucosa , as opposed to the junctional epithelium around teeth which originates from the reduced enamel epithelium .

58. Structurally the peri implant epithelium closely resembles the junctional epithelium around teeth Marker molecules involved in the defense mechanisms against the bacterial challenge are also expressed in the peri-implant epithelium . Eg : t- PA , ICAM-1, and a cytokeratin profile .

59. DIFFERENCES NATURAL TEETH IMPLANT DEVELOPMENT REDUCED ENAMEL EPITHELIUM ORAL EPITHELIUM THICKNESS TAPERS APICALLY THICKER ORGANELLES NUMEROUS FEWER GINGIVAL FIBERS ARRANGED PERPENDICULAR TO TOOTH SURCAE PARALLEL TO TOOTH SURFACE BIOLOGIC WIDTH 2.04 3-4

60. ROLE OF JUNCTIONAL EPITHELIUM IN PASSIVE ERUPTION Passive eruption is the exposure of the teeth by apical migration of the gingiva. STAGE 1 The teeth reach the line of occlusion. The junctional epithelium and base of the gingival sulcus are on the enamel.

61. STAGE 2 The junctional epithelium proliferates so that part is on the cementum and part is on the enamel. The base of the sulcus is still on the enamel.

62. STAGE 3 The entire junctional epithelium is on the cementum, and the base of the sulcus is at the cementoenamel junction.

63. STAGE 4 The junctional epithelium has proliferated farther on the cementum. The base of the sulcus is on the cementum, a portion of which is exposed. Proliferation of the junctional epithelium onto the root is accompanied by degeneration of gingival and periodontal ligament fibers and their detachment from the tooth.

64. CONCLUSION Junction epithelium is important because of its anatomic location. It is a site of host bacterial interaction in the initiation of periodontal disease. Conversion of junctional epithelium to pocket epithelium is considered as a hallmark in the initiation of periodontitis. Hence , a thorough knowledge of junctional epithelium is essential to prevent the initiation of periodontal disease.

65. REFERENCES Carranza’s Clinical periodontology-11 th edition Carranza’s Clinical periodontology- 13 th edition Clinical periodontology and Implant dentistry-Jan Lindhe , 6 th edition Orbans Oral histology and embryology DD Bosshardt and NP Lang. The Junctional Epithelium: from health to disease. J Dent Res 2005.

66. Marja T Pollanen , Jukka I Salonen, Veli - Jukka Uitto . Structure and function of the tooth–epithelial interface in health and disease . Periodontology 2000. 2003 ; 31:12–31 . Masaki Shimono , Tatsuya Ishikawa , Yasunobu Enokiya , Takashi Muramatsu et al. Biological characteristics of the junctional epithelium . Journal of Electron Microscopy .2003; 52(6): 627–639. Hubert E. Schroeder and Max A. Listgarten . The Junctional Epithelium: From Strength to Defense . J Dent Res . 2003; 82(3):158- 161 Anindya Priya Saha , Sananda Saha , Somadutta Mitra . Junctional Epithelium: A dynamic seal around the tooth Journal of Applied Dental and Medical Sciences . 2018 ; 4(3): 2454-2288