Nitric Oxide (NO), Intermediary NO Products and their Effect on thePathogenesis of Osteoarthritis

Overview

The inflammatory process and its contribution to the progression of osteoarthritis (OA) is probablymuch more important than assumed formerly. Interleukin-1 (IL-1) and tumour necrosis factor-α(TNF-α), the proinflammatory cytokines enhance the destructive processes in cartilage not only inRA but also in OA patients. Both of these cytokines are also capable of inducing the production ofnitric oxide (NO) in chondrocytes. NO is a reactive radical considered to be one of the inflammatorymediators which is synthesized via the oxidation of arginine by a family of nitric oxide synthases(NOS).We differentiate the constitutive (endothelial,ecNOS andneuronal,ncNOS)and the inducible(iNOS) isoforms. NO is a multifunctional molecule that mediates various biological processesespecially relaxation of smooth muscles, inflammation and host defense mechanisms against pathogens.Proinflammatory effects are vasodilatation, oedema, cytotoxicity and the mediation of cytokine-dependent processes that can lead to tissue destruction. On the other hand, production of NOby endothelial cell NOS serves antiinflammatory function by preventing the adhesion and releaseof oxidantsby activated neutrophils.NOinhibits cellular respirationandATPsynthesis, particularlyunder condition of low oxygen tension, which is found in the compartment of joint cavities. Thiseffect of NO on the energy metabolism is accompanied by the suppression of proteoglycan synthesisand up-regulation of stress-induced proteins by chondrocytes. In this paper we try to describevarious roles of nitric oxide, intermediate products of NO, its contribution to cartilage destructionand finally potential therapeutic implications of NO inhibition in patients with OA.

Key words:
osteoarthritis, nitric oxide, nitric oxide synthases