title: PPARγ is involved in the hyperglycemia-induced inflammatory responses and collagen degradation in human chondrocytes and diabetic mouse cartilages.
abstract: Diabetic hyperglycemia has been suggested to play a role in osteoarthritis. Peroxisome proliferator-activated receptor-γ (PPARγ) was implicated in several pathological conditions including diabetes and inflammation. The detailed effects and mechanisms of hyperglycemia on cartilage damage still need to be clarified. Here, we investigated the role of PPARγ in hyperglycemia-triggered chondrocyte/cartilage damages using a human chondrocyte culture model and a diabetic mouse model. Human chondrocytes were cultured and treated with high concentration of glucose (30 mM) to mimic hyperglycemia in the presence or absence of pioglitazone, a PPARγ agonist. Streptozotocin (STZ) was used to induce mouse diabetes. Our data showed that high glucose induced the protein expressions of cyclooxygenase-2 (COX-2) and production of prostaglandin-E2 (PGE2 ), interleukin-6 (IL-6), and metalloproteinase-13 (MMP-13), but decreased the protein expression of collagen II and PPARγ in human chondrocytes. These alterations in high glucose-treated human chondrocytes could be reversed by pioglitazone in a dose-dependent manner. Moreover, pioglitazone administration could also significantly reverse the hyperglycemia, formation of AGEs, productions of IL-6 and MMP-13, and cartilage damage in STZ-induced diabetic mice. Taken together, these findings suggest that hyperglycemia down-regulates PPARγ expression and induces inflammatory and catabolic responses in human chondrocytes and diabetic mouse cartilages.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ding-Cheng
authors.initials: DC
authors.lastname: Chan
authors.forename: Kuo-Cheng
authors.initials: KC
authors.lastname: Lan
authors.forename: Ching-Chia
authors.initials: CC
authors.lastname: Wang
authors.forename: Chang-Mu
authors.initials: CM
authors.lastname: Chen
authors.forename: Sung-Chuan
authors.initials: SC
authors.lastname: Chao
authors.forename: Keh-Sung
authors.initials: KS
authors.lastname: Tsai
authors.forename: Rong-Sen
authors.initials: RS
authors.lastname: Yang
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D019902:Chondrocytes / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007249:Inflammation / Q000209:etiology*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D047495:PPAR gamma / Q000502:physiology*; D000077205:Pioglitazone; D013311:Streptozocin; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D013311:Streptozocin; D003094:Collagen; D053509:Matrix Metalloproteinase 13; D015232:Dinoprostone; D000077205:Pioglitazone
keywords: PPARγ; chondrocyte; collagen; diabetes; osteoarthritis