title: 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.
  
  
  METHODS
  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.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: M-H
authors.initials: MH
authors.lastname: Moon
authors.forename: J-K
authors.initials: JK
authors.lastname: Jeong
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Lee
authors.forename: J-W
authors.initials: JW
authors.lastname: Seol
authors.forename: C J
authors.initials: CJ
authors.lastname: Jackson
authors.forename: S-Y
authors.initials: SY
authors.lastname: Park
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016328:NF-kappa B; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D015232:Dinoprostone; D000077185:Resveratrol