The Role of PPARγ in Advanced Glycation End Products-Induced Inflammatory Response in Human Chondrocytes

• Published in: PloS one Vol. 10; no. 5; p. e0125776
• Main Authors: Ma, Chi, Zhang, Ying, Li, Yu-qing, Chen, Cheng, Cai, Wei, Zeng, Yue-lin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.05.2015; Public Library of Science (PLoS)
• Subjects: Adult; Advanced glycosylation end products; Age; Arthritis; Biocompatibility; Biomedical materials; Cartilage, Articular - cytology; Cells, Cultured; Chondrocytes; Chondrocytes - drug effects; Chondrocytes - metabolism; Collagenase 3; Cytosol; Down-regulation; Female; Gene expression; Glycation End Products, Advanced - pharmacology; Glycosylation; Homeostasis; Human behavior; Humans; Immunoglobulins; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Inflammatory response; Inhibitors; Interleukin 1; Interleukin-1 - metabolism; JNK protein; Kinases; Male; MAP kinase; Matrix Metalloproteinase 13 - metabolism; NF-κB protein; Orthopedics; Osteoarthritis; Penicillin; Peroxisome proliferator-activated receptors; Pharmacology; Pioglitazone; PPAR gamma - agonists; PPAR gamma - metabolism; Proteins; Receptor mechanisms; Receptors; Signal transduction; Signaling; Thiazolidinediones - metabolism; Thiazolidinediones - pharmacology; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Western blotting
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125776

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. 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. 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. 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.