Effects of some nonsteroidal antiinflammatory drugs on proteoglycan metabolism and organization in canine articular cartilage

Abstract

The effects on proteoglycan metabolism and aggregation of several nonsteroidal antiinflammatory drugs commonly used in the treatment of arthritis were examined in cultures of normal canine articular cartilage. Fenoprofen and ibuprofen inhibited net proteoglycan synthesis in a concentration-dependent fashion. At concentrations in the culture medium comparable to plasma concentrations seen in patients after oral administration in humans, net proteoglycan synthesis in the presence of these drugs averaged 72% and 86% of the control values, respectively (P < 0.01). In contrast, indomethacin and sulindac sulfoxide had no effect on proteoglycan synthesis, while sulindac sulfide stimulated synthesis in a non-concentration dependent fashion (average, 13%). In the presence of ibuprofen or sulindac sulfide, catabolism of sulfated glycosaminoglycans was the same as that in control cartilage, while fenoprofen decreased the rate of degradation slightly. The proportion of newly synthesized proteoglycans existing as aggregates and the average hydrodynamic size of disaggregated proteoglycans were unaffected by ibuprofen, indomethacin, sulindac sulfide, or sulindac sulfoxide. Fenoprofen, on the other hand, interfered with the ability of the cartilage hyaluronic acid to interact with proteoglycans to form aggregates, whereas it had no effect on the in vitro association of proteoglycans with hyaluronic acid from umbilical cord.