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Regulation of collagenase gene expression in synovial cells.

The metalloproteinase collagenase that is synthesized and secreted by synovial cells is responsible for the large amount of connective tissue destruction seen in rheumatoid arthritis. We have used a model system of cultured rabbit synovial fibroblasts to better understand mechanisms controlling both the induction and suppression of collagenase synthesis. Induction of collagenase requires an increase in collagenase mRNA and concomitantly, suppression of collagenase synthesis by retinoids and glucocorticoids is accompanied by a decrease in collagenase mRNA. Another metalloproteinase, activator, which is responsible for the activation of latent procollagenase and which has gelatinolytic ability, is coordinately regulated with collagenase. We conclude that there may exist a family of metalloproteinases that is important in the modulation of connective tissues and that is coordinately regulated at the level of mRNA.