Nitric oxide and proteoglycan biosynthesis by human articular chondrocytes in alginate culture

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Abstract
Interleukin‐1α and β induced the production of large amounts of nitric oxide by normal, human articular chondrocytes in alginate culture; at the same time the biosynthesis of proteoglycan was strongly suppressed. In a dose‐dependent manner, N G‐monomethyl‐l‐arginine both inhibited nitric oxide formation and relieved the suppression of proteoglycan synthesis. However concentrations of N G‐monomethyl‐l‐arginine which completely prevented nitric oxide production only partially restored proteoglycan biosynthesis, even at low doses of interleukin‐1 where suppression of proteoglycan synthesis was modest. The organic donor of nitric oxide, S‐nitrosyl‐acetyl‐d,l‐ penicillamine also inhibited proteoglycan biosynthesis, but not as extensively as interleukin‐1. These data suggest that interleukin‐1 suppresses synthesis of the cartilaginous matrix through more than one mechanism, at least one of which is dependent upon the production of nitric oxide.