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http://dx.doi.org/10.4062/biomolther.2018.132

Inhibition of the Expression of Matrix Metalloproteinases in Articular Chondrocytes by Resveratrol through Affecting Nuclear Factor-Kappa B Signaling Pathway  

Kang, Dong-Geun (Department of Orthopaedic Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine)
Lee, Hyun Jae (Smith Liberal Arts College and Department of Addiction Science, Graduate School, Sahmyook University)
Lee, Choong Jae (Department of Pharmacology, School of Medicine, Chungnam National University)
Park, Jin Sung (Department of Orthopaedic Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine)
Publication Information
Biomolecules & Therapeutics / v.26, no.6, 2018 , pp. 560-567 More about this Journal
Abstract
In the present study, we tried to examine whether resveratrol regulates the expression of matrix metalloproteinases (MMPs) through affecting nuclear factor-kappa B ($NF-{\kappa}B$) in articular chondrocytes. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-${\beta}$ ($IL-1{\beta}$)-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 $IL-1{\beta}$-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 $IL-1{\beta}$-induced $NF-{\kappa}B$ 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 $IL-1{\beta}$induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa $B{\alpha}$ ($I{\kappa}B{\alpha}$); (4) resveratrol inhibited $IL-1{\beta}$-induced phosphorylation and nuclear translocation of $NF-{\kappa}B$ 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 $NF-{\kappa}B$ by directly acting on articular chondrocytes.
Keywords
Resveratrol; Chondrocytes; MMPs; Osteoarthritis;
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