Studies on the release of proteolytic enzymes during synovium-induced cartilage breakdown in vitro and the actions of anti-inflammatory drugs.

Pig articular cartilage, overlaid with a minced preparation of synovium from the same joint, underwent extensive matrix degradation during a two-week culture period. This degradation was associated with de novo synthesis by the synovium of specific neutral proteoglycan- and collagen-degrading enzymes. Both enzymes exhibited neutral pH optima, and were inhibited by serum and the metal ion chelators EGTA and 1,10-phenanthroline. The neutral proteoglycanase cleaved the core protein of isolated proteoglycan. The effects of some anti-inflammatory drugs on synovial enzyme production and cartilage metabolism were investigated. The steroids, dexamethasone and prednisolone, inhibited production of both enzymes whereas the non-steroidal anti-inflammatory drugs (NSAID's), flurbiprofen and indomethacin, slightly increased medium enzyme levels. Flurbiprofen and indomethacin had no effect on the extent of synovium-mediated cartilage degradation as assessed histologically. Inhibition by the steroids of synovial collagenase production correlated with inhibition of cartilage collagen breakdown, whereas inhibition of synovial proteoglycanase production did not prevent extensive proteoglycan breakdown. Experiments using radiotracer techniques indicated that dexamethasone, whilst partially inhibiting synovium-mediated proteoglycan degradation, severely inhibited cartilage proteoglycan synthesis thus resulting in net proteoglycan loss.