COLLAGENASE-3 (MATRIX METALLOPROTEINASE-13) EXPRESSION IS INDUCED IN ORAL MUCOSAL EPITHELIUM DURING CHRONIC INFLAMMATION

Increased proliferation of mucosal epithelium during inflammation is a ssociated with degradation of subepithelial connective tissue matrix a nd local invasion of the epithelial cells. Here we have studied, wheth er collagenase-3 (MMP-13), a collagenolytic matrix metalloproteinase w ith an exceptionally wide substrate specificity, is expressed in the e pithelium of chronically inflamed mucosa, Examination of human gingiva l tissue sections from subjects with chronic adult periodontitis with in situ hybridization revealed marked expression of MMP-13 in basal ce lls of some epithelial rete ridges expanding into connective tissue. I mmunohistochemical staining demonstrated that these cells also express ed strongly laminin-5, suggesting that they are actively migrating cel ls. A strong signal for MMP-13 mRNA was occasionally also noted in the suprabasal epithelial cells facing the gingival pocket, whereas no co llagenase-1 (MMP-1) mRNA was detected in any areas of the epithelium, MMP-13 expression was also detected in fibroblastlike cells associated with collagen fibers of the inflamed subepithelial connective tissue. In organ culture of human oral mucosa, MMP-13 mRNA expression was obs erved in epithelial cells growing into connective tissue of the specim ens. Regulation of MMP-13 expression was examined in cultured normal n onkeratinizing epithelial cells isolated from porcine periodontal liga ment. In these cells, MMP-13 expression at the mRNA and protein level was potently enhanced (up to sixfold) by tumor necrosis factor-alpha t ransforming growth factor-beta(1), and transforming growth factor-a an d by keratinocyte growth factor in the presence of heparin, In additio n, plating periodontal Ligament epithelial cells on type I collagen st imulated MMP-13 expression (sevenfold) as compared with cells grown on tissue culture plastic. The results of this study show, that expressi on of MMP-13 is specifically induced in undifferentiated epithelial ce lls during chronic inflammation due to exposure to cytokines and colla gen. Thus, it is likely that MMP-13 expression is instrumental in the subepithelial collagenolysis and local invasion of the activated mucos al epithelium into the connective tissue.