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

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. We have estimated NO production by Griess method, and PGE2 by RIA from the supernatants of articular cartilage obtained from osteoarthritis joints (OA-affected cartilage), rat chondrosarcomas (in ex vivo conditions) and bovine chondrocytes (stimulated with cytokines + endotoxin in vitro conditions) in the presence or absence of aspirin, indomethacin, sodium salicylate, tenidap and glucocorticoids. NO, which was spontaneously released in ex vivo conditions by OA-affected cartilage and rat chondrosarcomas (maintained in 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 PGE2 production 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 PGE2 production. Inhibition of NO in the cytokines + endotoxin stimulated bovine chondrocytes (like the human OA-affected cartilage) augmented PGE2 production. 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 characteristics of these cells that merits further investigation.