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The chemical biology of nitric oxide--an outsider's reflections about its role in osteoarthritis

Record type: Article

Excess formation of nitric oxide (NO) has been invoked in the development of osteoarthritis and blamed for triggering chondrocyte apoptosis and matrix destruction. Much of the evidence for a deleterious role of NO in disease progression has been obtained indirectly and inferred from the measurement of nitrite/nitrate and nitrotyrosine concentrations as well as iNOS expression in biopsy specimen, cartilage explants and cytokine-stimulated cells in culture. While these results clearly indicate an involvement of NO and suggest additional contributions from oxidative stress-related components they do not necessarily establish a cause/effect relationship. Many NO metabolites are not mere dosimeters of local NO production but elicit potent down-stream effects in their own right. Moreover, oxygen tension and other experimental conditions typical of many in vitro studies would seem to be at odds with the particular situation in the joint. Recent insight into the chemical biology of NO, in particular with regard to cellular redox-regulation, mitochondrial signaling and nitration reactions, attest to a much richer network of chemical transformations and interactions with biological targets than hitherto assumed. In conjunction with the emerging biology of nitrite and nitrate this information challenges the validity of the long-held view that "too much NO" is contributing to disease progression. Instead, it suggests that part of the problem is a shift from NO to superoxide-dominated chemistries triggering changes in thiol-dependent redox signaling, hypoxia-induced gene expression and mitochondrial function. This essay aims to provide a glimpse into research areas that may hold promise for future investigations into the underlying causes of osteoarthritis.

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Citation

Feelisch, Martin (2008) The chemical biology of nitric oxide--an outsider's reflections about its role in osteoarthritis Osteoarthritis and Cartilage, 16, supplement 2, S3-S13. (doi:10.1016/S1063-4584(08)60007-2). (PMID:18794015).

More information

Published date: June 2008
Keywords: oxidative stress, redox regulation, chemical biology, nitrite
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337706
URI: http://eprints.soton.ac.uk/id/eprint/337706
ISSN: 1063-4584
PURE UUID: 4199cc5e-017a-45cc-b5de-55d35f5a0654
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

Catalogue record

Date deposited: 02 May 2012 14:04
Last modified: 18 Jul 2017 06:01

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