EFFECTS OF CERTAIN ANTIARTHRITIC AGENTS ON THE SYNTHESIS OF TYPE-II COLLAGEN AND GLYCOSAMINOGLYCANS IN RAT CHONDROSARCOMA CULTURES

Cartilage destruction is a characteristic feature of osteoarthritis. T reatment with certain nonsteroidal anti-inflammatory drugs could exace rbate cartilage destruction by impairing the synthesis of cartilage ma trix proteins, type II collagen and proteoglycan. In order to monitor the changes occurring in cartilage collagen synthesis, we developed a type II collagen specific ELISA. The effects of antiarthritic agents o n type II collagen and glycosaminoglycan synthesis were examined in ra t chondrosarcoma cultures. Drugs were added to the monolayer cultures and 4 days later the total type II collagen, as determined by the type II collagen ELISA, and glycosaminoglycan content, as measured by dime thylmethylene blue dye binding assay, was measured. All drugs except t iaprofenic acid decreased type II collagen synthesis by at least 40% a t 100 mu g/ml. Tiaprofenic acid at 1 mu g/ml increased type II collage n content by 54% of the controls. Glycosaminoglycan synthesis was decr eased by acetylsalicylic acid, diclofenac and tiaprofenac acid, at 50 mu g/ml or above. Indomethacin, naproxen and dexamethasone had no effe ct. Interestingly, tenidap stimulated the glycoaminoglycan synthesis b y 32% at 100 mu g/ml. We show that the combination of chondrosarcoma c ultures, type II collagen specific ELISA and dimethylmethylene blue dy e binding assay serves as a useful model for screening the effects of agents capable of modulating type II collagen and glycosaminoglycan sy nthesis.