Regulation of nitic oxide production by salicylates and tenidap in human OA-affected cartilage, rat chondrosarcomas and bovine chondrocytes

Objective: To examine the effects of non-steroidal anti-inflammatory drugs (NSAIDS) on nitric oxide (NO) and prostaglandin E2(PGE2) production in chondrocytes from three different species. Methods: We have estimated NO production by Griess method, and PGE2by RIA from the supernatant of articular cartilage obtained from osteoarthritis joints (OA-affected cartilage), rat chondrosarcomas (inex vivoconditions) and bovine chondrocytes (stimulated with cytokines+endotoxin inin vitroconditions) in the presence or absence of aspirin, indomethacin, sodium salicylate, tenidap and glucocorticoids. Results: NO, which was spontaneously released inex vivoconditions by OA-affected cartilage and rat chondrosarcomas (maintainedin vivo), was susceptible to inhibition by pharmacologically relevant concentrations of aspirin, sodium salicylate and tenidap, but not to concentrations of indomethacin or glucocorticoids that significantly inhibited PGE2production under the same conditions. Similarly, the production of NO by bovine chondrocytes grown in monolayer cultures that had been stimulated with cytokines+endotoxins (in vitro) to release both No and PGE2(at 48–72 h post stimulation), were inhibited by aspirin, sodium salicylate and tenidap, but not by indomethacin or glucocorticoids at concentrations sufficient to inhibit PGE2production. Inhibition of NO in the cytokines+endotoxin stimulated bovine chondrocytes (like the human OA-affected cartilage) augmented PGE2production. Conclusion: These experiments demonstrate that NO production by chondrocytes across species show a similar profile of susceptibility to inhibition by selected anti-inflammatory drugs. The insensitivity of NO production to glucocorticoids is an important characteristic of these cells that merits further investigation.