KMID : 0606920180260060560
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Biomolecules & Therapeutics 2018 Volume.26 No. 6 p.560 ~ p.567
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Inhibition of the Expression of Matrix Metalloproteinases in Articular Chondrocytes by Resveratrol through Affecting Nuclear Factor-Kappa B Signaling Pathway
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Kang Dong-Geun
Lee Hyun-Jae Lee Choong-Jae Park Jin-Sung
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Abstract
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In the present study, we tried to examine whether resveratrol regulates the expression of matrix metalloproteinases (MMPs) through affecting nuclear factor-kappa B (NF-¥êB) in articular chondrocytes. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-1¥â (IL-1¥â)-induced gene expression of MMP-3, MMP-1, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4), ADAMTS-5 and type II collagen. Effect of resveratrol on IL-1¥â-induced secretion of MMP-3 was investigated in rabbit articular chondrocytes using western blot analysis. To elucidate the action mechanism of resveratrol, effect of resveratrol on IL-1¥â-induced NF-¥êB signaling pathway was investigated in SW1353, a human chondrosarcoma cell line, by western blot analysis. The results were as follows: (1) resveratrol inhibited the gene expression of MMP-3, MMP-1, MMP-13, ADAMTS-4, and ADAMTS-5, but increased the gene expression of type II collagen; (2) resveratrol reduced the secretion of MMP-3; (3) resveratrol inhibited IL-1¥â-induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa B¥á (I¥êB¥á); (4) resveratrol inhibited IL-1¥â-induced phosphorylation and nuclear translocation of NF-¥êB p65. This, in turn, led to the down-regulation of gene expression of MMPs in SW1353 cells. These results suggest that resveratrol can regulate the expression of MMPs through affecting NF-¥êB by directly acting on articular chondrocytes.
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KEYWORD
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Resveratrol, Chondrocytes, MMPs, Osteoarthritis
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