title: Pioglitazone inhibits advanced glycation end product-induced TNF-α and MMP-13 expression via the antagonism of NF-κB activation in chondrocytes.
abstract: OBJECTIVE
  Advanced glycation end products (AGEs) play a pivotal role in the initiation and progression of osteoarthritis (OA). Peroxisome proliferator-activated receptor-γ (PPARγ) has been shown to exhibit anti-inflammatory and anticatabolic properties and to be protective in animal models of OA. This study was aimed to investigate the possible protective effect of the PPARγ agonist pioglitazone on AGE-induced chondrocyte damage.
  
  
  METHODS
  Cultured chondrocytes were stimulated with AGEs in the presence or absence of an antibody against the receptor for AGEs (anti-RAGE), an inhibitor of NF-κB (pyrrolidine dithiocarbamate) and pioglitazone. The RNA expression levels of TNF-α, matrix metalloproteinase (MMP)-13 and PPARγ were detected by RT-PCR. The expression of nuclear p65 was determined by Western blot analysis.
  
  
  RESULTS
  Upregulation of TNF-α and MMP-13 as well as downregulation of PPARγ were induced by AGEs in a time- and dose-dependent manner. The maximum effect was induced by 100 μg/ml AGEs. This effect can be inhibited by anti-RAGE. Pioglitazone dose-dependently inhibited the expression of TNF-α and MMP-13 induced by AGEs, which was combined with the inhibition of nuclear p65 expression.
  
  
  CONCLUSIONS
  The PPARγ agonist pioglitazone modulates TNF-α and MMP-13 expression in cultured rabbit chondrocytes via NF-κB signaling. It indicates that pioglitazone may have therapeutic potential in OA.
authors.affiliation: Department of Orthopedics, The 163rd Central Hospital of the People's Liberation Army, The Second Affiliated Hospital of Hunan Normal University, Changsha, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zeng
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Li
authors.forename: Wanchun
authors.initials: W
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000235:genetics; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D045162:Thiazolidinediones / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D053509:Matrix Metalloproteinase 13; D000077205:Pioglitazone