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-κB, whereas the presence of peroxynitrite – a redox derivative of NO – appears to enhance the inflammatory response by sustaining the nuclear localization of nuclear factor-κB. 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.

Highlights

  • Osteoarthritis (OA) is a complex disease with a number of underlying biochemical and physical causes

  • Proinflammatory mediators, including nitric oxide (NO), IL-1, tumor necrosis factor (TNF)-α, and prostaglandins, are all over-produced in chondrocytes harvested from patients with OA and help to perpetuate the inflammatory process

  • Mendes and colleagues [32] found that IL-1 stimulation resulted in an increase in both hydrogen peroxide and superoxide in bovine articular chondrocytes, only superoxide was required for nuclear factor-κB (NF-κB) activation and iNOS expression

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Summary

Introduction

Osteoarthritis (OA) is a complex disease with a number of underlying biochemical and physical causes. Proinflammatory mediators, including nitric oxide (NO), IL-1, tumor necrosis factor (TNF)-α, and prostaglandins, are all over-produced in chondrocytes harvested from patients with OA (as reviewed by Pelletier and coworkers [1]) and help to perpetuate the inflammatory process. NO concentrations are, significantly increased in the synovial fluid of a canine OA model [8] These findings, in combination with experiments described below, contribute to the prevailing hypothesis that NO is a proinflammatory and proapoptotic factor that, when present in excess, is detrimental to the joint and contributes to OA pathogenesis. Arthritis Research & Therapy Vol 10 Suppl 2 Abramson disability in OA These studies suggest that NO donors could be an asset in the treatment of OA. This article briefly reviews the literature describing a catabolic role for NO in cartilage and chondrocytes, and summarizes existing studies that may suggest alternative roles for NO in the joint

Introduction to nitric oxide
Conclusion
Findings
10. Murad F
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