title: The Role of PPARγ in Advanced Glycation End Products-Induced Inflammatory Response in Human Chondrocytes.
abstract: OBJECTIVE
  Advances made in the past ten years highlight the notion that peroxisome proliferator-activated receptors gamma (PPARγ) has protective properties in the pathophysiology of osteoarthritis (OA). The aim of this study was to define the roles of PPARγ in AGEs-induced inflammatory response in human chondrocytes.
  
  
  METHODS
  Primary human chondrocytes were stimulated with AGEs in the presence or absence of neutralizing antibody against RAGE (anti-RAGE), MAPK specific inhibitors and PPARγ agonist pioglitazone. The expression of IL-1, MMP-13, TNF-α, PPARγ, nuclear NF-κB p65 and cytosol IκBα was determined by western blotting and real-time PCR.
  
  
  RESULTS
  AGEs could enhance the expression of IL-1, TNF-α, and MMP-13, but the level of PPARγ was decreased in a time- and dose-dependent manner, which was inhibited by anti-RAGE, SB203580 (P38 MAPK specific inhibitor) and SP600125 (a selective inhibitor of JNK). PPARγ agonist pioglitazone could inhibit the effects of AGEs-induced inflammatory response and PPARγ down-regulation. In human chondrocytes, AGEs could induce cytosol IκBα degradation and increase the level of nuclear NF-κB p65, which was inhibited by PPARγ agonist pioglitazone.
  
  
  CONCLUSIONS
  In primary human chondrocytes, AGEs could down-regulate PPARγ expression and increase the inflammatory mediators, which could be reversed by PPARγ agonist pioglitazone. Activation of RAGE by AGEs triggers a cascade of downstream signaling, including MAPK JNK/ p38, PPARγ and NF-κB. Taken together, PPARγ could be a potential target for pharmacologic intervention in the treatment of OA.
authors.affiliation: Department of Orthopedics, 163 Central Hospital of the People's Liberation Army, the Second Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410003, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, 163 Central Hospital of the People's Liberation Army, the Second Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410003, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, 163 Central Hospital of the People's Liberation Army, the Second Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410003, China.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Orthopedics, 163 Central Hospital of the People's Liberation Army, the Second Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410003, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, 163 Central Hospital of the People's Liberation Army, the Second Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410003, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Orthopedics, 163 Central Hospital of the People's Liberation Army, the Second Affiliated Hospital of Hunan Normal University, Changsha, Hunan, 410003, China.
authors.forename: Yue-Lin
authors.initials: YL
authors.lastname: Zeng
mesh_terms: D000328:Adult; D002358:Cartilage, Articular / Q000166:cytology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D007375:Interleukin-1; D047495:PPAR gamma; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D053509:Matrix Metalloproteinase 13; D000077205:Pioglitazone