Effects of indomethacin on glycosaminoglycan metabolism in the development of experimental osteoarthritis in rabbits

Abstract

The effects of indomethacin on glycosaminoglycan (GAG) metabolism during the development of experimental osteoarthritis produced by the immobilization of the knee in extension were studied in adult rabbits. The rabbits received intraperitoneal injections of indomethacin (10 mg/kg) daily for 17 days. The GAG content of the samples taken from the articular and periarticular connective tissues of the knee was assayed from determinations of hexosamine and uronic acid concentrations following papain proteolysis and subsequent purification. The uptake of 35S-sulphate (calculated as DPM/μg galactosamine) was used as an indicator of the synthesis rate of sulphated GAGs. The controls comprised normal rabbits, rabbits treated with indomethacin, rabbits immobilized for 17 days, and the non-immobilized contralateral leg of the immobilized rabbits receiving indomethacin. Indomethacin treatment failed to inhibit the uptake of 35S-sulphate in rabbits. The concentration of chondroitin sulphates was normal or elevated in animals receiving indomethacin. The drug did not prevent the loss of GAGs from the weight-bearing cartilage of the immobilized knees, but in tibial marginal tissues it prevented the accumulation of GAGs to some extent.