Inhibition of the Expression of Matrix Metalloproteinases in Articular Chondrocytes by Resveratrol through Affecting Nuclear Factor-Kappa B Signaling Pathway.
10.4062/biomolther.2018.132
- Author:
Dong Geun KANG
1
;
Hyun Jae LEE
;
Choong Jae LEE
;
Jin Sung PARK
Author Information
1. Department of Orthopaedic Surgery, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon 51472, Republic of Korea.
- Publication Type:Original Article
- Keywords:
Resveratrol;
Chondrocytes;
MMPs;
Osteoarthritis
- MeSH:
Blotting, Western;
Cell Line;
Chondrocytes*;
Chondrosarcoma;
Collagen Type II;
Down-Regulation;
Gene Expression;
Humans;
Matrix Metalloproteinases*;
Osteoarthritis;
Phosphorylation;
Phosphotransferases;
Thrombospondins
- From:Biomolecules & Therapeutics
2018;26(6):560-567
- CountryRepublic of Korea
- Language:English
-
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.
