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  Česky / Czech version Čes. Revmatol., 11, 2003, No. 1, p. 42-50
 
Nitric Oxide (NO), Intermediary NO Products and their Effect on the Pathogenesis of Osteoarthritis 
Šenolt L., Pavelka K. 

Revmatologický ústav, Praha
 


Summary:

       The inflammatory process and its contribution to the progression of osteoarthritis (OA) is probably much 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 in RA but also in OA patients. Both of these cytokines are also capable of inducing the production of nitric oxide (NO) in chondrocytes. NO is a reactive radical considered to be one of the inflammatory mediators 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 processes especially 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 NO by endothelial cell NOS serves antiinflammatory function by preventing the adhesion and release of oxidantsby activated neutrophils.NOinhibits cellular respirationandATPsynthesis, particularly under condition of low oxygen tension, which is found in the compartment of joint cavities. This effect of NO on the energy metabolism is accompanied by the suppression of proteoglycan synthesis and up-regulation of stress-induced proteins by chondrocytes. In this paper we try to describe various roles of nitric oxide, intermediate products of NO, its contribution to cartilage destruction and finally potential therapeutic implications of NO inhibition in patients with OA.

        Key words: osteoarthritis, nitric oxide, nitric oxide synthases
       

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