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1
2
I. INTRODUCTION
Gingiva
Keratinization
II. GINGIVAL KERATINIZATION
Process
Control of keratinocyte differentiation
Cytoker...
IntroductionIntroduction
4
GINGIVA
 “Gingiva is the part of the oral mucosa that
covers the alveolar processes of the jaws and
surrounds the neck of...
Anatomically
 Free or Marginal
Gingiva.
 Attached Gingiva.
 Interdental Gingiva.
(Carranza 10th
ed)
6
 Keratinization can be defined as expression &
synthesis of keratin proteins in the basal layer
of cell,their chemical co...
 Also called as “CORNIFICATION”
 Differantiation process rather than degeneration
 Process of protein synthesis→Require...
PARAKERATINI Z ATION:
 the stratum corneum retains pkynotic nuclei and
 the keratohyaline granules are dispersed, not gi...
 
Only some areas of the outer gingival epithelium are
orthokeratinized the other gingival areas are covered by
parakerat...
 The outer surface of the free & attached gingiva is
covered by a keratinizing stratified squamous
epithelium.
 The prin...
12
 
 The basal layer is made up of cells that
synthesize DNA and undergo mitosis, thus
providing new cells. Most of the new...
 
 Cytoplasm of the basal cells contain widely dispersed
tonofilaments, also referred to as Cytokeratins which
are precur...
 The intercellular spaces - are large & distended;
thus desmosomes are made more prominent
& these cells are given a pric...
ODLAND BODIES:
16
 Cells are larger and flatter.
 Cells show increase in maturation.
 nuclei shows signs of degeneration and
pyknosis.
 ...
Thus,corneocytes are mainly formed by bundles of keratin tonofilaments
embedded in an amorphous matrix of filaggrin and su...
BIOCHEMICAL
PROPERTIES:
19
 Cells are very flat ,devoid of nuclei, full of
keratin filaments surrounded by a matrix may
be termed epithelial squamae...
21
FACTOR PROLIIFERATION DIFFERENTIATION
EGF ↑
KGF ↑↑
RETINOIDS ↑ ↓
CALCIUM ↑
TGF-α ↑
TGF-β ↓ ↑
α/β INTEGRINS+
LIGAND
↓
22
EPIDERMAL GROWTH FACTOR &
TRANSFORMING GROWTH FACTOR
23
KERATINOCYTE GROWTH FACTOR
24
RETINOIC ACID
25
CALCIUM
26
Non keratinized Keratinized
 1.basal
◦ Cuoidal ,columnar cells
◦ Separate tonofilaments
◦ Organelles
◦ Site of cell divis...
 Immunohistochemistry, gel electrophoresis, and immunoblot
techniques suggest that, keratin proteins are composed of
diff...
Cytokeratin proteins( CK )
 They are composed of different polypeptide subunits &numbered
in a sequence contrary to their...
 Keratin K1, K2and K10 to K12
-Specific for epidermal type differentiation.
-Expressed with high intensity in orthokerati...
31
ELECTRON
MICROSCOPY
32
 Keratinocytes are interconnected
by structures on the cell periphery
called desmosomes.
 They consist of two dense
atta...
34
 The main function of the gingival epithelium is to
protect the deep structures while allowing a
selective interchange wi...
 The Involucrin becomes cross linked (by the
enzyme transglutaminase) to form a thin (l0nm),
highly resistant, electron d...
 The keratinized gingiva on the facial aspect of
teeth extend from gingival margin to MGJ. It is
often claimed that prese...
38
Width of the attached gingiva
Maxilla Mandible
Incisors premolars Incisors
3.5 to 4.5mm 1.9 mm 3.3 to 3.9mm 1.8 mm
prem...
 Resistance to products of inflammation.
 Gives support to the marginal gingiva
 Helps to withstand functional stress
...
40
 Keratinization serves as an epithelial barrier so
with decreased keratinization infection
susceptibility is increased.(S...
Rapid turnover of cells of keratinized epithelium
Keratinized layer is dehydrated to form hexagonal disks or squames
Squam...
 The immunohistochemical patterns of the
different keratin types, envelope proteins, and
filaggrin, change under normal o...
44
45
46
47
 Oral dysplasia is a premalignant lesion but some
cases respondto treatment or revert
spontaneously and therefore it is d...
 The desmosomes attachment plaques contain the
polypeptides desmoplakin I and II.
 Monoclonal antibodies to these polype...
 Accelarated turnover of cells is seen.
 K6, K16 and K17 were detected suprabasally in
psoriatic epidermis
 As keratins...
 Hyperkeratotic lesions - lichen planus and fibromas
showed aberrations in their Ck profile.
 extended expression of ker...
 parakeratotic epithelium markers (K4 and K13) were
detected but showed reduced expression in
orthokeratoses( K1 and K10)...
 Terminal differentiation markers, typical of cornified
epithelia (CK 1, 9, 10 and 11), were detected supra
basally in th...
 The mitotic index in patients with diabetes was
slightly lower, keratinization in the gingival
tissues for both groups w...
 The pattern of keratin expression of the
epithelium of pocket lining was found to be
essentially similar to normal JE.
P...
 dyshesive, dyskeratotic epithelial syndrome
caused by an abnormality in desmosomes and
gap junctions, involves the mucos...
Conclusion
57
Keratinization of gingiva is indespensable to
maintain its state of health.
Expression of cytokeratins is tissue specific
...
1. Clinical peridontology 8, 9,10th
edition – Carranza F.A., Michael G. Newman.
2. Oral Histology, Development, structure ...
11. Differentiation-dependent expression of keratins in human
oral epithelia J Invest Dermatol. 1986 Mar;86(3):249-54
12.E...
61
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Gingival keratinization ppt

  1. 1. 1
  2. 2. 2
  3. 3. I. INTRODUCTION Gingiva Keratinization II. GINGIVAL KERATINIZATION Process Control of keratinocyte differentiation Cytokeratins of oral mucosa Immuno chemical & electronmicroscopic picture III. KERATINIZED Vs NON KERATINIZED EPITHELIA IV. CLINICAL SIGNIFICANCE OF KERATINIZATION OF GINGIVA IN HEALTH & DISEASE V. KERATINIZATION OF GINGIVA IN DISEASE Diseases & conditions with altered keratinization Clinical co relations of altered keratinization with disease VI. CLINICAL IMPLICATIONS VII. CONCLUSION VIII. REFERENCES 3 CONTENTS:
  4. 4. IntroductionIntroduction 4
  5. 5. GINGIVA  “Gingiva is the part of the oral mucosa that covers the alveolar processes of the jaws and surrounds the neck of the teeth. (Carranza 1o th ed)  ““The fibrous investing tissue, covered by keratinized epithelium, which immediately surrounds a tooth and is contiguous with its periodontal ligament and with the mucosal tissues of the mouth.”.” A A P 1992A A P 1992 5
  6. 6. Anatomically  Free or Marginal Gingiva.  Attached Gingiva.  Interdental Gingiva. (Carranza 10th ed) 6
  7. 7.  Keratinization can be defined as expression & synthesis of keratin proteins in the basal layer of cell,their chemical composition in the upper layer & their interaction with keratohyalin granules & formation of filamentous matrix structure in the interior of corneocyte & strenghtening of the envelope. (The process of keratinization of gingival epithelium. ;The Journal of western society of periodontology; 1979) KERATINIZATION 7
  8. 8.  Also called as “CORNIFICATION”  Differantiation process rather than degeneration  Process of protein synthesis→Requires energy→dependent on functional cells containing nucleus & organelles  Cell migrate from basal to superficial→biochemical & morphological events takeplace  Cytoplasmic proteins tranform into keratin filaments  Cytoplasm & nucleus both decompose. 8
  9. 9. PARAKERATINI Z ATION:  the stratum corneum retains pkynotic nuclei and  the keratohyaline granules are dispersed, not giving rise to stratum granulosum. NON-KERATINIZED EPITHELIUM  neither granulosum nor corneum strata and  superficial cells have viable nuclei. ORTHOKERATINIZATION:  similar to that of skin with no nuclei in the stratum corneum and  a well-defined stratum granulosum.   9
  10. 10.   Only some areas of the outer gingival epithelium are orthokeratinized the other gingival areas are covered by parakeratinized or nonkeratinized epithelium.  In the gingival epithelium ,15% area is orthokeratinised other areas are covered by parakeratinised ;75%or nonkeratinised epithelium 10%  Diurnal cycle of keratinization activity is seen between 12pm to 4am 10
  11. 11.  The outer surface of the free & attached gingiva is covered by a keratinizing stratified squamous epithelium.  The principal cell type of the gingival epithelium, as well as of other stratified squamous is keratinocyte.  Keratinizing oral epithelium has four cell layers:  Basal, Stratum basale,  Spinous, Stratum spinosum  Granular Stratum granulosum and  Cornified,Stratum corneum GINGIVA L KERATINI Z ATION 11
  12. 12. 12
  13. 13.    The basal layer is made up of cells that synthesize DNA and undergo mitosis, thus providing new cells. Most of the new cells are generated in the basal layer. 13
  14. 14.    Cytoplasm of the basal cells contain widely dispersed tonofilaments, also referred to as Cytokeratins which are precurser of keratin’and in some way are attached to the attachment plaques.  ribosomes & rough endoplasmic reticulum are found-, indicative of protein synthesizing activity. .   ( Orbans 10th ed) 14
  15. 15.  The intercellular spaces - are large & distended; thus desmosomes are made more prominent & these cells are given a prickly appearance.  The spinous (prickle) cells resemble a cockleburr or sticker that has each spine ending at a desomosome.  Spinous cells are the most active in protein synthesis.  Contains numerous dense granules – keratinosome or Odland bodies ( Orbans 10th ed) 2 Stratum spinosum 15
  16. 16. ODLAND BODIES: 16
  17. 17.  Cells are larger and flatter.  Cells show increase in maturation.  nuclei shows signs of degeneration and pyknosis.  C ytoplasm is predominantly occupied by the tonofilaments & tonofibrils.  C ells contain large no’s of small granules – keratohyalin granules- these granules help to form the matrix for the numerous keratin fibers found in the superficial layers ( Orbans 10th ed) 17
  18. 18. Thus,corneocytes are mainly formed by bundles of keratin tonofilaments embedded in an amorphous matrix of filaggrin and surrounded by a resistant envelope under the cell membrane. 18
  19. 19. BIOCHEMICAL PROPERTIES: 19
  20. 20.  Cells are very flat ,devoid of nuclei, full of keratin filaments surrounded by a matrix may be termed epithelial squamae & are dehydrated.  does not synthesize protein.  These cells are shed (the process of desquamation), necessitating constant turnover of epithelial cells.  Str corn. provides the mechanical protective function to the mucosa.  Varies in thickness (upto 20 cells).  Keratinocytes increase in volume in each successive layer. ( Lindhe 5th ed) 20
  21. 21. 21
  22. 22. FACTOR PROLIIFERATION DIFFERENTIATION EGF ↑ KGF ↑↑ RETINOIDS ↑ ↓ CALCIUM ↑ TGF-α ↑ TGF-β ↓ ↑ α/β INTEGRINS+ LIGAND ↓ 22
  23. 23. EPIDERMAL GROWTH FACTOR & TRANSFORMING GROWTH FACTOR 23
  24. 24. KERATINOCYTE GROWTH FACTOR 24
  25. 25. RETINOIC ACID 25
  26. 26. CALCIUM 26
  27. 27. Non keratinized Keratinized  1.basal ◦ Cuoidal ,columnar cells ◦ Separate tonofilaments ◦ Organelles ◦ Site of cell division  2.prickle ◦ Large ovoid cells ◦ Dispersed tonofilaments ◦ Organelles ◦ Membrane coated granules-upper layers ◦ filaments ↑  3.intermediate. ◦ Sligtly flattened cells ◦ Dispersed tonofilaments & glycogen  4.Superficial ◦ Same as intermediate layer ◦ Nuclei are persistant  1.basal ◦ Cuoidal ,columnar cells ◦ Bundles of tonofilaments ◦ Organelles ◦ Site of cell division  2.prickle ◦ Large ovoid cells ◦ Conspicous tonofilament bundles ◦ Organelles ◦ Membrane coated granules-upper layers ◦ filaments ↑  3.granular ◦ flattened cells-contain keratohyalin granules ◦ Thickening of cell memb-granule fuse with cell membrane  4. corneum ◦ F lattened & ◦ Dehydrated cells ◦ All organelles are lost ◦ P acked with fibrillar material ◦ Nuceus if present-pyknotic 27
  28. 28.  Immunohistochemistry, gel electrophoresis, and immunoblot techniques suggest that, keratin proteins are composed of different polypeptide subunits characterized by their isoelectric points and molecular weights.  Numbered →their molecular weights. IMMUNOHISTOCHEMISTRY 28
  29. 29. Cytokeratin proteins( CK )  They are composed of different polypeptide subunits &numbered in a sequence contrary to their molecular weights. eg. K19- mol wt. 40 kDa – present at basal cells 2 gene family  Type I  Acidic  No. 9-20  high tissue specificity  they are always in pairs - type I is smaller than type II by about 8kDa TYPE II Basic No.1-8 29
  30. 30.  Keratin K1, K2and K10 to K12 -Specific for epidermal type differentiation. -Expressed with high intensity in orthokeratinized areas & less intensity in parakeratinized areas.  K6 and K16 -Characteristic of highly proliferative epithelia.  K5 and K14 -Stratification specific cytokeratines -Both are present in outer epithelia.  K19 -Absent in orthokeratinized areas. 30
  31. 31. 31
  32. 32. ELECTRON MICROSCOPY 32
  33. 33.  Keratinocytes are interconnected by structures on the cell periphery called desmosomes.  They consist of two dense attachment plates into which tonofibrils insert and an intermediate,electron-dense line in the extracellular compartment  Tonofilaments →morphologic expression of the cytoskeleton of keratin proteins→ radiate in brush like fashion from the attachment plaques in the cytoplasm of the cells  cytoplasmic projections resembling microvillie extend into the intercellular space 33
  34. 34. 34
  35. 35.  The main function of the gingival epithelium is to protect the deep structures while allowing a selective interchange with the oral environment. This is achieved by proliferation and differentiation of keratinocyte  The gingiva is exposed to heavy mechanical stresses during mastication.moreover the epithelial attachment of tooth is relatively weak & susceptible to injury ;can cause permanent damage. Thus keratinization of gingiva may afford relative protection. 35
  36. 36.  The Involucrin becomes cross linked (by the enzyme transglutaminase) to form a thin (l0nm), highly resistant, electron dense, cornified envelop just beneath the plasma membrane.  The keratin is also strongly cross-linked by disulphide bonds, contributing to the mechanical and chemical resistance of the layer. 36
  37. 37.  The keratinized gingiva on the facial aspect of teeth extend from gingival margin to MGJ. It is often claimed that presence of zone of atleast 2mm of keratinized gingiva is necessary for the maintainance of gingival health.(Gottsegon 1954,Naber 1954,Glickman 1992,Corn 1973,Schuluger 1977).  Lang & Loe(1992) support this whereas others authors (Miyasatto 1977,Grey & Besmimoulin 1980, Doffman et al 1980) suggests that there is no requirement for minimal width-provided accumalation of plaque is inhibited. 37
  38. 38. 38 Width of the attached gingiva Maxilla Mandible Incisors premolars Incisors 3.5 to 4.5mm 1.9 mm 3.3 to 3.9mm 1.8 mm premolar ATTACHED GINGIVA
  39. 39.  Resistance to products of inflammation.  Gives support to the marginal gingiva  Helps to withstand functional stress  Resistance to tensional stresses.  Provides solid base for movable alveolar mucosa  To dissipate the pull on the gingival margin created by the muscles of the adjacent alveolar mucosa. ( Sullivan et al 1968)  Helps to prevent soft tissue recession and attachment loss  Helps in connective tissue attachment 39
  40. 40. 40
  41. 41.  Keratinization serves as an epithelial barrier so with decreased keratinization infection susceptibility is increased.(Scheman;1989)  There is increased susceptibility to masticatory force damage due to decreased resistance to functional & tensional stresses. SEQULAE: 41
  42. 42. Rapid turnover of cells of keratinized epithelium Keratinized layer is dehydrated to form hexagonal disks or squames Squames are cont. lost by desquamation & replaced by cells of underlying layers Rapid clearance-limits colonization & invasion of epithelial surface by pathogenic micro organisms Including common oral fungus candida albicans Thus with↓keratinization↑chances of infection are there 42
  43. 43.  The immunohistochemical patterns of the different keratin types, envelope proteins, and filaggrin, change under normal or pathologic stimuli, modifying the keratinization process THIS COULD BE OF DIAGNOSTIC VALUE. 43
  44. 44. 44
  45. 45. 45
  46. 46. 46
  47. 47. 47
  48. 48.  Oral dysplasia is a premalignant lesion but some cases respondto treatment or revert spontaneously and therefore it is desirableto define molecular changes that would allow pathologists toidentify the highest risk lesions.  Moreover K8,k18 &K19 – found in highly proliferative epithelia is seen in oral leukoplakia & SCC.(Su et al, 1996)- they can be used for diagnosis 48
  49. 49.  The desmosomes attachment plaques contain the polypeptides desmoplakin I and II.  Monoclonal antibodies to these polypeptides can be used to detect an epithelial tumor by immunofluoroscent microscopy. 49
  50. 50.  Accelarated turnover of cells is seen.  K6, K16 and K17 were detected suprabasally in psoriatic epidermis  As keratins K6, K16 and K17 are expressed in keratinocyte hyperproliferation, Thus it signifies the same. PSORIASIS Leigh et al; 1995 50
  51. 51.  Hyperkeratotic lesions - lichen planus and fibromas showed aberrations in their Ck profile.  extended expression of keratinization marker Ck 10, Ck 14 and Ck 16 in the suprabasal compartment.  The stratification markers Cks 4 and 13 showed a decreased expression.  Help to to characterize benign mucosal lesions with dysplasia and might be helpful for distinguishing these lesions from potentially malignant ones. BENIGN LESIONS OF THE ORAL MUCOSA Volden et al 1999 51
  52. 52.  parakeratotic epithelium markers (K4 and K13) were detected but showed reduced expression in orthokeratoses( K1 and K10), particularly in the presence of lymphocytes.  study showed an alteration in the pattern of differentiation-specific keratins, although involvement of the lymphocytic infiltrate (Interferon γ )in OLP resulted in further gene modulation.  Thus, the pattern of keratin gene expression may be altered in response to frictional/smoking stimuli or immune-mediated mechanisms ORAL NON-DYSPLASTIC KERATOSES AND LICHEN PLANUS Bloor et al 2000 52
  53. 53.  Terminal differentiation markers, typical of cornified epithelia (CK 1, 9, 10 and 11), were detected supra basally in the snuff user's keratosis but not in the normal control epithelium.  The results show that use of oral snuff causes some alterations in the CK expression pattern of the affected epithelium. Whether the alterations are indicative of a premalignant change is, however, uncertain. Effect of snuff and smoking on cytokeratin expression in oral mucosa Luomanen et al ;1997 53
  54. 54.  The mitotic index in patients with diabetes was slightly lower, keratinization in the gingival tissues for both groups was essentially identical. COMPARISON OF KERATINOCYTE PROLIFERATION IN DIABETIC AND NON-DIABETIC INFLAMED GINGIVA Gükhan Açikgoz ;2004 54
  55. 55.  The pattern of keratin expression of the epithelium of pocket lining was found to be essentially similar to normal JE. PATTERN OF CYTOKERATIN EXPRESSION IN THE EPITHELIUM OF INFLAMMED HUMAN GINGIVA & PERIODONTAL POCKET Mackenzie ;1993 55
  56. 56.  dyshesive, dyskeratotic epithelial syndrome caused by an abnormality in desmosomes and gap junctions, involves the mucosae, skin, hair, eyes, and lungs.  gingival sections showed a dyshesive epithelium with atrophy, dyskeratosis, lack of keratinization, and unusual cytoplasmic inclusions.  patients with hereditary mucoepithelial dysplasia have numerous skin problems and are susceptible to recurrent infection . HEREDITARY MUCOEPITHELIAL DYSPLASIA Scheman;1989 56
  57. 57. Conclusion 57
  58. 58. Keratinization of gingiva is indespensable to maintain its state of health. Expression of cytokeratins is tissue specific and even strata specific & any alteration in this suspects breach from its state of normalcy. It is desirableto define these molecular changes that would allow pathologists to identify the highest risk lesions & thus it holds promising future in diagnosis…. 58
  59. 59. 1. Clinical peridontology 8, 9,10th edition – Carranza F.A., Michael G. Newman. 2. Oral Histology, Development, structure and function – A.R. Tencate, 5th edition 3. Periodontics ;Elly and masson. 4. Orbans Oral Histology and Embryology – S.N. Bhaskar, 10th edition. 5. Clinical Periodontology and Implant Dentistry – Jan Lindhe, 4th edition. 6. Relation between width of attached gingiva & health. JP 1972 7. Oral cells & tissues .Garant 8. Comparison of Keratinocyte Proliferation in Diabetic and Non-Diabetic Inflamed Gingiva ;JP July 2004, Vol. 75, No. 7, Pages 989-994 9. Hereditary mucoepithelial dysplasia. Case report and review of the literature J Am Acad Dermatol. 1989 Aug;21(2 Pt 2):351-7 10. Patterns of cytokeratin expression in the epithelia of inflamed human gingiva and periodontal pockets J Periodontal Res. 1993 Jan;28(1):49-59 59 REFERENCES:
  60. 60. 11. Differentiation-dependent expression of keratins in human oral epithelia J Invest Dermatol. 1986 Mar;86(3):249-54 12.Effect of snuff on cytokeratin expression in oral vestibular sulcus epithelium J Oral Pathol Med. 1997 Mar;26(3):110-6 13.Expression of intermediate filament proteins in benign lesions of the oral mucosa Eur Arch Otorhinolaryngol. 1999;256(10):514-9 14.Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro Br J Dermatol. 1995 Oct;133(4):501-11 15.Gene expression of differentiation-specific keratins (K4, K13, K1 and K10) in oral non-dysplastic keratoses and lichen planus J Oral Pathol Med. 2000 Sep;29(8):376-84 16.The process of keratinization of gingival epithelium. The Journal of western society of periodontology; vol 27; no.3 pg: 72-85 1979 60
  61. 61. 61
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