Pathogenesis Of Oral Submucous Firosis

Pathogenesis Of Oral Submucous Firosis

Answer. Basically, pathogenesis of OSMF consists of disturbance in collagen metabolism via TGF β. The whole procedure is described as:

Initial Event Of Disease Process

According to P.Rajalitha, S.Vali (2005) initial event of the disease process is, oral mucosa which is in direct contact with betel quid (tobacco + areca nut + slaked lime + catechu and condominents) because of the habit which is the meAns of constant irritation.

Major areca nut alkaloids are arecoline,arecaidine, arecolidine, guacoline and guacine. Out of all these arecoline is most abundant.

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These alkaloids undergo nitrosation and give rise to N nitrosamines which have cytotoxic effects on cells.

Important flvonoid components of areca nut are tannins and catechins.

So all these alkaloids,flvonoids and microtrauma produced by friction of coarse fiers of areca nut leads to chronic inflammatory process which is characterized by presence of inflammatory cells, i.e.

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T cells and macrophages, these cells release and/or stimulate synthesis of various cytokines and growth factors.

Increased susceptibility among individuals who are anemic due to iron or vitamin B12 deficiencies.

It is because of increased fragility of mucosa by which there is more betel quid absorption.

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Collagen production pathway as regulated by tgF β

Transforming growth factor-β (TGF–β) is a growth factor which regulate the collagen production pathway, it has autocrine activity.

TGF–β activate procollagen genes which lead to production of more procollagen.

TGF–β also increases secretion of procollagen C proteinase (PCP) and procollagen N proteinase (PNP) both of these are needed for conversion of procollagen to collagen fibrils.

• In oral submucous fibrosis, there is increase in cross linking of collagen which results to increase in insoluble form.
• This is facilitated by increased activity and production of key enzyme Lysyl oxidase (LOX).
• PCP and bone morphogenetic protein 1 and increased copper in betel quid stimulate the activity of LOX which produces increase collagen which is insoluble.
• Flavonoids increases the cross linking of collagen fiers. These all steps lead to increase in collagen production.
• TGF β strongly promote the expression of LOX both at mRNA and protein levels in various cell lines.
• LOX activity is important in formation of insoluble collagen due to cross-linking.
• Process of cross linking provides tensile strength and mechanical properties to fiers as well as makes collagen fiers resistant to proteolysis.

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Collagen Degradation pathway as regulated by tgF–β

There are also two main events modulated by TGF–β which also decreases collagen degradation, i.e. activation of tissue inhibitor of matrix metalloproteinase gene (TIMPs) and activation of plasminogen activator inhibitor (PAI) gene.

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Collagen degradation pathway as regulated by TGF-β activates genes for TIMPs and so more TIMP is formed.

Now this inhibit activated collagenase enzyme which is necessary for degradation of collagen.

It also activate genefor PAI which is the inhibitor of plasminogen activator,so there is no plasmin formation.

Plasmin is needed for the conversion of procollagenase to active form of collagenase and absence of plasmin lead to absence of active collagenase.

Flavonoids inhibit collagenase activity.

Reduction in activity and levels of collagenase result in decrease in collagen degradation.

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Overall Effect Of TgF–Β Pathway

So, overall effect of activated TGF–β pathway is that there is an increase in collagen production and cross­linking (insoluble form) along with decrease in collagen degradation.

This produces an increased collagen deposition in subepithelial connective tissue layer of oral mucosa causing oral submucous fibrosis.