title: Nitric oxide in inflammation and pain associated with osteoarthritis.
abstract: Osteoarthritis (OA) is a degenerative disease involving chondrocytes, cartilage and other joint tissues, and has a number of underlying causes, including both biochemical and mechanical factors. Although proinflammatory factors including nitric oxide (NO) are associated with OA, there is recent evidence suggesting that NO and its redox derivatives may also play protective roles in the joint. However, the mechanisms that underlie the development and progression of OA are not completely understood. Experiments have demonstrated that NO plays a catabolic role in the development of OA and mediates the inflammatory response, is involved in the degradation of matrix metalloproteinases, inhibits the synthesis of both collagen and proteoglycans, and helps to mediate apoptosis. However, there is also evidence that in cultured chondrocytes the addition of exogenous NO may inhibit proinflammatory activation by preventing the nuclear localization of the transcription factor nuclear factor-kappaB, whereas the presence of peroxynitrite--a redox derivative of NO--appears to enhance the inflammatory response by sustaining the nuclear localization of nuclear factor-kappaB. In addition, under some conditions exogenous NO can stimulate collagen synthesis in cultured rat fibroblasts and human tendon cells. The protective roles of NO in multiple cell types, along with the opposing activities in cultured chondrocytes, suggest that NO may play additional protective roles in chondrocyte function. NO and its derivatives have a similarly complicated involvement in nociception and pain, which may contribute to the functional disability of OA. Further research may help to elucidate a potential role for NO-donating agents in the management of OA.
authors.affiliation: Division of Rheumatology, Hospital for Joint Diseases, New York University School of Medicine, 301 E, 17th Street, New York, NY 10003, USA. stevenb.abramson@nyumc.org
authors.forename: Steven B
authors.initials: SB
authors.lastname: Abramson
mesh_terms: D002358:Cartilage, Articular / Q000503:physiopathology; D019902:Chondrocytes / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D010003:Osteoarthritis / Q000150:complications / Q000503:physiopathology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology*
chemical_list: D009569:Nitric Oxide