Interactions in connective tissues involving monocyte/macrophages and control of production of proteinases and proteinase inhibitors.
McGuire MK., Meats JE., Ebsworth NM., Gowen M., Murphy G., Reynolds JJ., Russell RG.
Using human articular chondrocytes in monolayer culture as an experimental system, we have been studying mechanisms of control of production and activity of neutral proteases which degrade connective tissue matrices. Soluble factors from cultured human blood mononuclear cells (MCF) or synovial fragment cultures (SF) stimulate the production of collagenase and proteoglycanase by chondrocytes. Chondrocytes also release a collagenase inhibitor (mol. wt. 26-31,000), which is similar to the tissue inhibitor of metalloproteinases (TIMP) synthesized by cultured mammalian tissues and this is reduced in cultures exposed to MCF or SF. Retinol and dexamethasone partially inhibit the factor-stimulated collagenase, but increase the amount of inhibitor, restoring it to control levels in the presence of MCF or SF. The effects of these agents in cellular interactions in vitro will be discussed in relation to their possible roles in the control of connective tissue turnover in vivo.