NITRIC-OXIDE MEDIATES INTERLEUKIN-1 INDUCED-INHIBITION OF GLYCOSAMINOGLYCAN SYNTHESIS IN RAT ARTICULAR-CARTILAGE

INTERLEUKIN-1 beta (IL-1) is a key mediator of cartilage matrix degrad ation in osteoarthritis and rheumatoid arthritis. It was found that th e IL-1-induced suppression of glycosaminoglycan (GAG) synthesis in rat articular cartilage occurred simultaneously with the accumulation of nitrite (a metabolite of nitric oxide (NO) in aqueous milieu) in the c ulture medium. NO-synthase inhibitors, L-NMMA and L-NIO, inhibited bot h these IL-1 effects. Dexamethasone suppressed GAG synthesis additivel y to IL-1, but did not alter nitrite accumulation. Three NO-donors (GE A 3175, SNAP and SIN-1) also had an inhibitory effect on cartilage GAG synthesis. Therefore, it is concluded that IL-1 induced suppression o f GAG synthesis in rat articular cartilage is mediated by the producti on of NO.