CYTOKINE CONTROL OF INTERSTITIAL COLLAGENASE AND COLLAGENASE-3 GENE-EXPRESSION IN HUMAN CHONDROCYTES

Human collagenase-3 expression, previously seen only in a breast tumor tissue, is here shown to be expressed in primary human chondrocytes d erived from the joint tissue and in transformed human chondrocytes. It s mRNA is inducible by the inflammatory cytokines interleukin-1 beta p lus tumor necrosis factor-alpha, but not by phorbol 12-myristate 13-ac etate and only slightly by the growth factors platelet-derived growth factor and epidermal growth factor. Human synovial fibroblasts, anothe r prominent cell type in the joint tissue, do not produce collagenase- 3 message, Expression of the murine collagenase, which is possibly the counterpart of human collagenase-3, is induced by interleukin-1 beta plus tumor necrosis factor-alpha, and its full induction requires the presence of the transcription factor, c-FOS, This family of transcript ion factors also plays a role in induction of human collagenase-3, sin ce it binds to the AP-1 site of this matrix metalloproteinase.