Biomol Ther.  2018 Nov;26(6):560-567. 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

Affiliations
  • 1Department of Orthopaedic Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon 51472, Republic of Korea.
  • 2Smith Liberal Arts College and Department of Addiction Science, Graduate School, Sahmyook University, Seoul 01795, Republic of Korea.
  • 3Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon 35015, Republic of Korea.
  • 4Department of Orthopaedic Surgery, Institute of Health Sciences, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju 52727, Republic of Korea. jsparkler@naver.com

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-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.

Keyword

Resveratrol; Chondrocytes; MMPs; Osteoarthritis

MeSH Terms

Blotting, Western
Cell Line
Chondrocytes*
Chondrosarcoma
Collagen Type II
Down-Regulation
Gene Expression
Humans
Matrix Metalloproteinases*
Osteoarthritis
Phosphorylation
Phosphotransferases
Thrombospondins
Collagen Type II
Matrix Metalloproteinases
Phosphotransferases
Thrombospondins
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