Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis.
Articular chondrocyte production of nitric oxide (NO) and other inflammatory mediators, such as eicosanoids and cytokines, are increased in human osteoarthritis. The excessive production of nitric oxide inhibits matrix synthesis and promotes its degradation. Furthermore, by reacting with oxidants such as superoxide anion, nitric oxide promotes cellular injury and renders the chondrocyte susceptible to cytokine-induced apoptosis. PGE(2) exerts anabolic and catabolic effects on chondrocytes, depending on the microenvironment and physiologic condition. The increased expression of inducible NOS (iNOS) and cyclo-oxygenase-2 (COX-2) in OA chondrocytes is largely due to the increased expression of pro-inflammatory cytokines, particularly IL-1, which act in an autocrine/paracrine fashion to perpetuate a catabolic state that leads to progressive destruction of articular cartilage. The initiating factors for the production of inflammatory mediators include altered biomechanical forces; their continued production may be augmented by an increase in extracellular matrix proteins acting through ligation of surface integrins.
Abramson
S B
SB
Department of Medicine, Division of Rheumatology NYU School of Medicine, New York, NY 10003, USA. steven.abramson@med.nyu.edu
Attur
M
M
Amin
A R
AR
Clancy
R
R
D002358:Cartilage, Articular / Q000378:metabolism; D016207:Cytokines / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D010003:Osteoarthritis / Q000209:etiology* / Q000503:physiopathology
D016207:Cytokines; D018836:Inflammation Mediators; D009569:Nitric Oxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II