Characterization of collagenase, other metallo-proteinases and an inhibitor (TIMP) produced by human synovium and cartilage in culture.

1. Explants of human synovium from normal, rheumatoid and osteoarthritic subjects produced proteinases in culture that could degrade connective tissue macromolecules at neutral pH. 2. The proteinases detected in the media were predominantly of the class requiring metal ions for activity, and occurred in either partially or wholly latent forms. Activation could be achieved by treatment with either trypsin or the organo-mercurial, 4-aminophenylmercuric acetate. 3. Explants of both normal and osteoarthritic synovium produced an inhibitor of collagenase in the early days of culture, similar to that previously described for rabbit tissues. In contrast, no free inhibitor could be detected in the media of rheumatoid synovial cultures. 4. Explants of normal human articular cartilage produced latent collagenase and free inhibitor in culture. 5. These findings suggest that the activity of tissue-derived metallo-proteinases may be controlled by locally synthesized inhibitors, by mechanisms analogous to those already described for rabbit model systems. Changes in the synthesis and degradation of inhibitor could be important in human diseases in which destruction of connective tissue is a prominent feature.