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II. GINGIVAL KERATINIZATION
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
“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
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
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
Cytoplasm & nucleus both decompose.
PARAKERATINI Z ATION:
the stratum corneum retains pkynotic nuclei and
the keratohyaline granules are dispersed, not giving
rise to stratum granulosum.
neither granulosum nor corneum strata and
superficial cells have viable nuclei.
similar to that of skin with no nuclei in the stratum
a well-defined stratum granulosum.
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
Diurnal cycle of keratinization activity is seen between 12pm
The outer surface of the free & attached gingiva is
covered by a keratinizing stratified squamous
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
KERATINI Z ATION
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.
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
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
2 Stratum spinosum
Cells are larger and flatter.
Cells show increase in maturation.
nuclei shows signs of degeneration and
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
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.
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
Non keratinized Keratinized
◦ Cuoidal ,columnar cells
◦ Separate tonofilaments
◦ Site of cell division
◦ Large ovoid cells
◦ Dispersed tonofilaments
◦ Membrane coated granules-upper
◦ filaments ↑
◦ Sligtly flattened cells
◦ Dispersed tonofilaments &
◦ Same as intermediate layer
◦ Nuclei are persistant
◦ Cuoidal ,columnar cells
◦ Bundles of tonofilaments
◦ Site of cell division
◦ Large ovoid cells
◦ Conspicous tonofilament bundles
◦ Membrane coated granules-upper
◦ filaments ↑
◦ flattened cells-contain
◦ Thickening of cell memb-granule
fuse with cell membrane
◦ F lattened &
◦ Dehydrated cells
◦ All organelles are lost
◦ P acked with fibrillar material
◦ Nuceus if present-pyknotic
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.
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
high tissue specificity
they are always in pairs - type I is smaller than type II by about
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.
-Absent in orthokeratinized areas.
Keratinocytes are interconnected
by structures on the cell periphery
They consist of two dense
attachment plates into which
tonofibrils insert and an
line in the extracellular
expression of the cytoskeleton
of keratin proteins→ radiate in
brush like fashion from the
in the cytoplasm of the cells
resembling microvillie extend
into the intercellular space 33
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
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
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
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
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.
Width of the attached gingiva
Incisors premolars Incisors
3.5 to 4.5mm 1.9 mm 3.3 to 3.9mm 1.8 mm
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
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
Helps in connective tissue attachment
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.
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
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.
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
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
Accelarated turnover of cells is seen.
K6, K16 and K17 were detected suprabasally in
As keratins K6, K16 and K17 are expressed in
keratinocyte hyperproliferation, Thus it
signifies the same.
Leigh et al; 1995
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
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
Volden et al 1999
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
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,
Effect of snuff and smoking on
cytokeratin expression in oral mucosa
Luomanen et al ;1997
The mitotic index in patients with diabetes was
slightly lower, keratinization in the gingival
tissues for both groups was essentially
COMPARISON OF KERATINOCYTE
PROLIFERATION IN DIABETIC AND
NON-DIABETIC INFLAMED GINGIVA
Gükhan Açikgoz ;2004
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
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
patients with hereditary mucoepithelial
dysplasia have numerous skin problems and are
susceptible to recurrent infection .
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
It is desirableto define these molecular
changes that would allow pathologists to
identify the highest risk lesions & thus it
holds promising future in diagnosis….
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