SIRT1, a class III histone deacetylase, regulates TNF-α-induced inflammation in human chondrocytes.

Abstract

OBJECTIVE:

The present study was performed to elucidate the possible role of SIRT1 signaling in joint inflammation in human articular chondrocytes.

DESIGN:

Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were performed to detect gene products and proteins involved in tumor necrosis factor α (TNF-α)-induced inflammation and cartilage degradation in human primary chondrocytes. Matrix metalloproteinase (MMP)-2 and MMP-9 activity was evaluated by gelatin zymography. Overexpression and knockdown of SIRT1 were also performed to investigate whether SIRT1 is associated with the anti-inflammatory activity of resveratrol in chondrocytes.

RESULTS:

Resveratrol dose-dependently inhibited TNF-α-induced cyclooxygenase-2 (COX-2), MMP-1, MMP-3, MMP-13 and PGE(2) production in human chondrocytes. Moreover, MMP-2 and MMP-9 activity was increased by treatment with TNF-α; however, SIRT1 activation decreased the proinflammatory effects induced by TNF-α. In addition, treatment of SIRT1 activator and overexpression of SIRT1 inhibited the expression and activation of the main proinflammatory regulator NF-κB, which was increased by TNF-α. When SIRT1 was overexpressed in chondrocytes, the anti-inflammatory action of SIRT1 was similar to that exerted by resveratrol.

CONCLUSIONS:

SIRT1 activation deacetylates and inactivates NF-κB, and thereby, exerts an anti-inflammatory effect on chondrocytes, suggesting that SIRT1 activators could be explored as potential treatments for arthritis.

• Authors: M-H Moon, J-K Jeong, Y-J Lee, J-W Seol, C J Jackson, S-Y Park
• Journal: Osteoarthritis and cartilage (Osteoarthritis Cartilage) Vol. 21 Issue 3 Pg. 470-80 (Mar 2013) ISSN: 1522-9653 [Electronic] England
• PMID: 23257246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• NF-kappa B
• Stilbenes
• Tumor Necrosis Factor-alpha
• Cyclooxygenase 2
• Matrix Metalloproteinase 13
• Matrix Metalloproteinase 3
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• Matrix Metalloproteinase 1
• SIRT1 protein, human
• Sirtuin 1
• Dinoprostone
• Resveratrol

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Blotting, Western
• Cartilage, Articular (metabolism)
• Chondrocytes (drug effects, metabolism)
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Humans
• Matrix Metalloproteinase 1 (metabolism)
• Matrix Metalloproteinase 13 (metabolism)
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 3 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• NF-kappa B (metabolism)
• Osteoarthritis, Knee (metabolism)
• Real-Time Polymerase Chain Reaction
• Resveratrol
• Reverse Transcriptase Polymerase Chain Reaction
• Sirtuin 1 (metabolism)
• Stilbenes (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)