Biomol Ther 2018; 26(6): 560-567
Inhibition of the Expression of Matrix Metalloproteinases in Articular Chondrocytes by Resveratrol through Affecting Nuclear Factor-Kappa B Signaling Pathway
Dong-Geun Kang1,†, Hyun Jae Lee2,†, Choong Jae Lee3,* and Jin Sung Park4,*
1Department of Orthopaedic Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon 51472,
2Smith Liberal Arts College and Department of Addiction Science, Graduate School, Sahmyook University, Seoul 01795,
3Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon 35015,
4Department of Orthopaedic Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 52727, Republic of Korea
E-mail: (Park JS), (Lee CJ)
Tel: +82-55-750-8858 (Park JS), +82-42-580-8255 (Lee CJ)
Fax: +82-55-750-8104 (Park JS), +82-42-585-6627 (Lee CJ)
†The first two authors contributed equally to this work.
Received: July 16, 2018; Revised: August 30, 2018; Accepted: September 18, 2018; Published online: November 1, 2018.
© The Korean Society of Applied Pharmacology. All rights reserved.

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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-κB) in articular chondrocytes. Rabbit articular chondrocytes were cultured in a monolayer, and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure interleukin-1β (IL-1β)-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-1β-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-1β-induced NF-κB 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-1β-induced activation (phosphorylation) of inhibitory kappa B kinase (IKK), and thus phosphorylation and degradation of inhibitory kappa Bα (IκBα); (4) resveratrol inhibited IL-1β-induced phosphorylation and nuclear translocation of NF-κB 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-κB by directly acting on articular chondrocytes.
Keywords: Resveratrol, Chondrocytes, MMPs, Osteoarthritis

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Funding Information
  • National Research Foundation of Korea(NRF)
      NRF-2014R1A6A1029617, NRF-2017R1C1B1005126
  • Ministry of Education(Ministry of Education of the Republic of Korea)

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