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• W1986373312 abstract "ObjectiveTo simultaneously study the effect of a selective cyclooxygenase-2 (COX-2) inhibitor and that of a classic non-steroidal anti-inflammatory drug (NSAID) on the expression of pro-inflammatory genes in the cartilage of patients with severe knee osteoarthritis (OA) and in cultured human OA chondrocytes.MethodsA 3-month clinical trial was carried out on 30 patients with severe knee OA scheduled for knee replacement surgery. Patients were randomized into two groups: patients treated with celecoxib (CBX) and patients treated with aceclofenac (ACF). OA patients who did not want to be treated served as the control group. After surgery, cartilage was processed for molecular biology studies. We also employed cultured chondrocytes from different OA patients to examine NSAID effects on pro-inflammatory gene expression in cells stimulated with interleukin (IL)-1β.ResultsBoth CBX and ACF inhibited COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and inducible nitric oxide synthase (iNOS) synthesis in the articular cartilage of OA patients. In cultured chondrocytes, both NSAID decreased COX-2 and mPGES-1 synthesis and prostaglandin E2 (PGE2) release induced by IL-1β, while no effect was observed on nitric oxide or iNOS synthesis. In OA patients, only CBX decreased tumor necrosis factor alpha and IL-1β expression in the cartilage, while both NSAID diminished IL-1β induced cytokine synthesis in cultured OA chondrocytes.ConclusionsBoth NSAID diminished PGE2 release and induced a decrease in COX-2 and mPGES-1 synthesis in the cartilage from OA patients and in OA chondrocytes. These data suggest that prolonged therapy with PGE2 blocking agents decreases PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating COX-2 and mPGES-1 synthesis in the cartilage. However, CBX and ACF seem to have a different anti-inflammatory profile in controlling pro-inflammatory gene expression in the cartilage." @default.
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• W1986373312 date "2008-12-01" @default.
• W1986373312 modified "2023-10-17" @default.
• W1986373312 title "Long-term NSAID treatment directly decreases COX-2 and mPGES-1 production in the articular cartilage of patients with osteoarthritis" @default.
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• W1986373312 doi "https://doi.org/10.1016/j.joca.2008.04.022" @default.
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