PPARγ is involved in the hyperglycemia-induced inflammatory responses and collagen degradation in human chondrocytes and diabetic mouse cartilages
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Journal Volume
33
Journal Issue
3
Pages
373
Date Issued
2015-03
Author(s)
Chen, Ying-Ju
Lan, Kuo-Cheng
Liu, Shing-Hwa
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.
Subjects
PPARγ; chondrocyte; collagen; diabetes; osteoarthritis
SDGs
Other Subjects
collagenase 3; cyclooxygenase 2; glucose; interleukin 6; peroxisome proliferator activated receptor gamma; pioglitazone; prostaglandin E2; streptozocin; 2,4 thiazolidinedione derivative; collagen; collagenase 3; peroxisome proliferator activated receptor gamma; pioglitazone; prostaglandin E2; animal cell; animal experiment; animal model; Article; articular cartilage; cartilage cell; cell culture; collagen degradation; dose response; glucose blood level; human; human cell; hyperglycemia; inflammation; male; mouse; nonhuman; priority journal; protein expression; protein function; streptozotocin-induced diabetes mellitus; adult; aged; animal; biosynthesis; cartilage; complication; experimental diabetes mellitus; hyperglycemia; inflammation; Institute for Cancer Research mouse; metabolism; middle aged; physiology; Adult; Aged; Animals; Cartilage; Chondrocytes; Collagen; Diabetes Mellitus, Experimental; Dinoprostone; Humans; Hyperglycemia; Inflammation; Male; Matrix Metalloproteinase 13; Mice; Mice, Inbred ICR; Middle Aged; PPAR gamma; Streptozocin; Thiazolidinediones
Publisher
WILEY
Type
journal article