Objective-The first complement component C1s was reported to have novel functions to degrade matrix components, besides its activities in the classic complement pathway. This study explores participation of C1s in articular cartilage degradation in rheumatoid arthritis (RA). Methods-Normal articular cartilage (n=6) and cartilage obtained from joints with RA (n=15) and osteoarthritis (OA, n=10) were immunostained using antiC1s monoclonal antibodies PG11, which recognises both active and inactive C1s, and M241, which is specifically reactive to activated C1s. The eVects of inflammatory cytokines on C1s production by human articular chondrocytes were also examined by sandwich ELISA. Results-In normal articular cartilage, C1s was negative in staining with both PG11 and M241. In contrast, degenerating cartilage of RA was stained with PG11 (14 of 15 cases), and in most of the cases (13 of 15 cases) C1s was activated as revealed by M241 staining. In OA, C1s staining was restricted in severely degrading part of cartilage (5 of 10 cases), and even in that part C1s was not activated. In addition, C1s production by chondrocytes in vitro was increased by an inflammatory cytokine, tumour necrosis factor . Conclusion-These results suggest that C1s activated in degenerative cartilage matrix of RA but not in that of OA. C1s is thought to participate in the pathogenesis of RA through its collagenolytic activity in addition to the role in the classic cascade.

The activated first component of human complement, Cis, was shown to cleave type I and II collagen and gelatin. The proteolytic activity was heat labile and was inhibited by a monoclonal antibody (M241) which recognized light chain of active human Cls or by a serine protease inhibitor, DFP, but not by a chelating agent.

Expression of the first complement component (C1s) has been examined in chondrocytes of hamster epiphyseal cartilage during development and fracture healing. C1s is immunostained with anti-hamster C1s monoclonal antibody, PG11. The C1s staining increases in accordance with chondrocyte differentiation and reaches a maximal level in hypertrophic chondrocytes. This change is observed at both the tibia ossification center and at the callus in which the replacement of cartilage by bone marrow takes place. The concomitant increase of C1s and chondrocyte hypertrophy has been confirmed by RNA blot and by in situ hybridization. These results, in addition to previous findings on C1s collagenolytic and gelatinolytic activities, suggest C1s participation in cartilage remodeling.

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