Nitric oxide enhances cyclooxygenase activity in articular cartilage

Nitric oxide (NO) is a small messenger molecule synthesized by a family of enzymes, the nitric oxide synthases. Cyclooxygenases are a group of proinflammatory enzymes that release prostaglandins including prostaglandin E₂ (PGE₂). Both nitric oxide synthase and cyclooxygenase are involved in the inflammatory cascade of arthritis. However, the relationship between these two enzymes and their products has not been explored in articular cartilage. Here we show that in cultured bovine chondrocytes and explants of human osteoarthritic cartilage both nitric oxide synthase and cyclooxygenase activities were induced by the inflammatory mediators, lipopolysaccharide, and interleukin-1 or tumor necrosis factor-. When nitric oxide synthase activity was inhibited, PGE₂, synthesis was inhibited. NO donors also induced PGE₂ synthesis and NO scavengers inhibited cyclooxygenase activity. Taken together, these results support the concept that PGE₂ synthesis is directly related to NO formation and that NO may modulate cyclooxygenase activity in articular cartilage.accepted by W. B. van den BergFinalist in the 1995 Westinghouse Science Talent Search, the 1995 Otto Burgdorf Competition, and the 1995 St. Johns New York Symposium.