alexa Cyclooxygenase-2 and prostaglandins in articular tissues.


Molecular Biology: Open Access

Author(s): MartelPelletier J, Pelletier JP, Fahmi H

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Abstract OBJECTIVES: To provide an overview on: 1) the expression of cyclooxygenase (COX)-2 in articular tissues; 2) the role of prostaglandin E2 (PGE2) in these tissue functions; and 3) clinical trials with COX-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) (coxibs). METHODS: MEDLINE search was performed using the key words "cyclooxygenase," "prostaglandin," "osteoarthritis" (OA), and "rheumatoid arthritis" (RA). Selected publications related to clinical trials with coxibs also are included. RESULTS: COX-2 is upregulated in inflamed joint tissues and is responsible for elevated PGE2 production. The overexpression of COX-2 is likely induced by proinflammatory mediators such as interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF) alpha. However, the exact molecular mechanisms through which the expression of COX-2 is regulated remain to be elucidated. Several studies suggest that PGE2 is involved in inflammation, apoptosis, angiogenesis, and possibly structural changes that characterize arthritic diseases. NSAIDs are prescribed for the treatment of OA and RA and provide effective relief from symptoms; however, serious gastrointestinal complications occur with their use. The clinical efficacy of NSAIDs is primarily related to the inhibition of COX-2, whereas much of the toxicity is related to COX-1 inhibition. Selective COX-2 inhibitors (coxibs) that spare COX-1 at therapeutic doses are more effective than placebo and as effective as other NSAIDs for relief of symptoms of OA and RA, and have significantly improved gastrointestinal safety and tolerability. However, some studies showed that COX-2-selective inhibitors still have classic NSAID complications. CONCLUSIONS: Overexpression of COX-2 protein in articular tissues is a characteristic feature of arthritic diseases. However, the molecular mechanisms involved in the regulation of COX-2 expression and activity are still unclear. Elucidating the mechanisms of COX-2 expression and PGE2 production and action will help identify novel and more selective potential drug targets in the treatment of arthritic diseases.
This article was published in Semin Arthritis Rheum and referenced in Molecular Biology: Open Access

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