ELASTASE ACTIVITY IN CARTILAGE EXTRACTS AND SYNOVIAL-FLUIDS FROM SUBJECTS WITH OSTEOARTHRITIS OR RHEUMATOID-ARTHRITIS - THE PROMINENT ROLE OF METALLOPROTEINASES

Objective: Polymorphonuclear leukocyte (PMN) elastase is able to degra de the extra-cellular matrix components of cartilage. However, in vitr o several proteinases can degrade elastin. The purpose of this study w as to evaluate the role of the serine proteinases and metalloproteinas es in the elastase activity measured in cartilage extracts from patien ts with osteoarthritis (OA), as well as in synovial fluid (SF) from pa tients with rheumatoid arthritis (RA) and OA. Methods: Elastase activi ty was determined using synthetic low molecular weight substrates and radiolabelled insoluble elastin. Aminophenyl mercuric acetate was used to activate the prometalloproteinases. Results: Elastase activity, me asured using synthetic substrates, was higher in RASF (0.76 + 0.03 mu U/ml, n = 12) than in OASF (0.14 + 0.04 mu U/ml, n = 12) (p < 0.001). This activity was inhibited by metal chelating agents: 86% inhibition in OA and 75% inhibition in RA. However, in RASF the inhibitor of seri ne proteinase (PMSF) also induced a 40% inhibition. Elastase activity, measured using radiolabelled elastin, in OASF and RASF samples and in OA cartilage extract was very low, but increased following activation by mercurial agents. Again this activity was inhibited by metal chela ting agents. Conclusions: Taken together these results indicate that e lastase activity (measured by standard methods) in OA and RASF is main ly due to metalloenzymes.