Deficiency in collagen and fibronectin phagocytosis by human buccal mucosa fibroblasts in vitro as a possible mechanism for oral submucous fibrosis

Abstract

Oral submucous fibrosis (OSF), a chronic oral mucosal condition commonly found in south Asians, is a disorder characterized by a quantitative as well as a qualitative alteration of collagen deposition within the subepithelial layer of the oral mucosa. Since degradation of collagen by fibroblast phagocytosis is an important pathway for physiological remodelling of soft connective tissues, we have investigated phagocytosis of collagen‐ and fibronectin‐coated latex beads by fibroblast cultures with an in vitro model system. Coated fluorescent latex beads were incubated with human oral mucosa fibroblasts and the fluorescence associated with internalized beads was measured by flow cytometry. Cells from normal tissues that had been incubated with beads for 16 h contained a mean of 75% collagen phagocytic cells and 70% fibronectin phagocytic cells; however, about 15% and 10% of phagocytic cells individually contained more than twice the mean number of beads per cell. In contrast, cells from OSF tissues exhibited a 40% reduction of the proportions of collagen phagocytic cells (mean=35%) and a 48% decrease of the proportions of fibronectin phagocytic cells (mean=22%), none of the cells having a high number of beads as compared to normal fibroblasts. OSF lesions appear to contain fibroblasts with marked deficiencies in collagen and fibronectin phagocytosis. To investigate if inhibition of phagocytosis could be demonstrated in vitro, normal fibroblast cultures were incubated with areca nut alkaloids (arecoline, arecaidine). The cultures had a dose‐dependent reduction in the proportions of phagocytic cells. On the other hand, corticosteroid used in the treatment of OSF exhibited a dose‐dependent enhancement in the proportion of phagocytic cells. Therefore, our hypothesis for OSF, although over‐simplified, is that betel nut alkaloids (arecoline, arecaidine) inhibit fibroblast phagocytosis and this provides a mechanism for the development of OSF. The benefit of a local intralesional injection of corticosteroid is also possibly, at least in part, through an enhancement of fibroblast collagen phagocytosis.

Therapeutic Interventions in Oral Submucous Fibrosis: An Experimental and Clinical Study

“…As OSF shows a gross imbalance in ECM remodeling, this putative mechanism was investigated in vitro [29]. A decrease of the phagocytic activity of fibroblasts in OSF patients when compared with the normal persons has been earlier reported [31]. The number of phagocytic cells and phagocytic activity in cultured human oral fibroblasts from OSF site was lower than the fibroblasts from the normal regions of the same person.…”

Mast Cell Density in Oral Submucous Fibrosis : A Possible Role in Pathogenesis

“…It affects the mucosa of any part of oral cavity and occasionally extending into the pharynx and esophagus. (1,2) The pathogenesis of the disease is not well established. Since its first description various etiopathological concepts have been put forward such as spices (chilies), nutritional deficiencies, genetic susceptibility, lysyl oxidase, autoimmunity and one of the most accepted is areca nut usage.…”

Clinico-Pathological Evaluation and Correlation of Stages of Oral Submucous Fibrosis with Different Habits

“…In the areca nut chewers the Lysl oxidize activity is unregulated to alter fibroblast metabolism producing more collagen. This may add to the conclusion of the occurrence of OSF due to the products leaching out from areca nut causes OSF and not from those leaching out from tobacco [1,27].…”

“…The occurrence of OSF was seen significantly in those having one or the other forms of areca nut which showed that the product which leaches out from areca nut would be responsible for the development of OSF [1,27]. People having tobacco alone have never been seen to have OSF.…”