Comparative immunolocalization studies of collagenase 1 and collagenase 3 production in the rheumatoid lesion, and by human chondrocytes and synoviocytes in vitro

The degradation of fibrillar type II collagen is a major feature ofcartilage destruction in rheumatoid arthritis (RA). Since collagenase 3 isproduced by chondrocytes and preferentially degrades type II cartilagecollagen, it seemed likely that this enzyme would have a prominent role inthe destruction of rheumatoid joints. Using immunolocalization techniques,we have examined and compared the production and distributions ofcollagenase 1 and collagenase 3 in cells and tissues derived fromrheumatoid knee arthroplasties. Primary cultures of chondrocytes stimulatedwith interleukin-1 beta showed that most of the cells produced collagenase1, whereas only a minority (approximately 5-10%) produced collagenase 3; afew chondrocytes demonstrated the co-ordinate production of both enzymes.Primary cultures of rheumatoid synoviocytes produced collagenase 1, but notcollagenase 3. Both enzymes were demonstrated in the rheumatoid lesion.Collagenase 1 was more commonly observed in both synovium and cartilage (22of the 28 specimens), was especially prominent at cartilage erosion sites,and most of the positive specimens demonstrated extracellular enzyme. Bycontrast, collagenase 3 was observed less frequently (7/28 specimens) andwas produced by relatively few chondrocytes and synovial cells, thisusually being much less than that observed for chondrocytes ofosteoarthritic cartilage. These observations suggest different regulatorymechanisms for the production of collagenases 1 and 3 in the rheumatoidlesion, and demonstrate that the distribution and production of collagenase1 are far more prevalent than those for collagenase 3.