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• W2019449067 abstract "<b>Background:</b> MMP-13 is one of the most important metalloproteases (MMP) involved in osteoarthritis. Licofelone, a novel dual inhibitor of cyclo-oxygenases (COX) and 5-lipoxygenase (5-LOX), can modulate MMP-13 production in human osteoarthritis chondrocytes. <b>Objective:</b> To evaluate the impact of licofelone on MMP-13 expression/production, promoter, and major MAP kinase signalling pathways and transcription factors. <b>Methods:</b> Human osteoarthritis chondrocytes were stimulated by interleukin 1β (IL1β) and treated with or without: licofelone (0.3, 1, or 3 μg/ml); NS-398 (10 μM; a specific COX-2 inhibitor); or BayX-1005 (10 μM; a specific 5-LOX inhibitor). MMP-13 synthesis was determined by specific enzyme linked immunosorbent assay, and expression by real time polymerase chain reaction. The effect of licofelone on the MMP-13 promoter was studied through transient transfection; dexamethasone (10⁻⁷ M) was used as comparison. The effect on IL1β induced MMP-13 signalling pathways was determined using specific ELISA for phosphorylated MAP kinases and transcription factors. <b>Results:</b> Licofelone dose dependently inhibited the IL1β stimulated production and expression of MMP-13. NS-398 and BayX-1005 had very little effect. Licofelone also inhibited MMP-13 transcription on each of the promoter constructs used. The licofelone inhibition was comparable to that obtained with dexamethasone. Licofelone had no effect on phosphorylated p44/42 or JNK1/2; however, it decreased phosphorylated c-jun and inhibited phosphorylated p38, CREB, and AP-1 activity. <b>Conclusions:</b> Licofelone inhibited MMP-13 production under proinflammatory conditions on human osteoarthritis chondrocytes, through inhibition of the p38/AP-1 pathway and the transcription factor CREB. This may explain some of the mechanisms whereby licofelone exerts its positive effect on osteoarthritic changes." @default.
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• W2019449067 date "2005-06-01" @default.
• W2019449067 modified "2023-09-30" @default.
• W2019449067 title "The regulation of human MMP-13 by licofelone, an inhibitor of cyclo-oxygenases and 5-lipoxygenase, in human osteoarthritic chondrocytes is mediated by the inhibition of the p38 MAP kinase signalling pathway" @default.
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• W2019449067 doi "https://doi.org/10.1136/ard.2004.026906" @default.
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