PPARγ is involved in the hyperglycemia‐induced inflammatory responses and collagen degradation in human chondrocytes and diabetic mouse cartilages

Journal of Orthopaedic Research - Tập 33 Số 3 - Trang 373-381 - 2015
Ying‐Ju Chen1, Ding‐Cheng Chan2, Kuo‐Cheng Lan3, Shyh‐Jye Chen4, Chang−Mu Chen5, S.-H. Chao3, Keh‐Sung Tsai6, Rong‐Sen Yang7, Shing‐Hwa Liu8,4,1
1Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan
2Department of Geriatrics and Gerontology, National Taiwan University Hospital, Taipei, Taiwan
3Department of Emergency Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan
4Department of Pediatrics, College of Medicine, National Taiwan University, Taipei, Taiwan
5Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
6Department of Laboratory Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
7Department of Orthopaedics, College of Medicine, National Taiwan University, Taipei, Taiwan
8Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan

Tóm tắt

ABSTRACTDiabetic 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. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???–???, 2015.

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Journal of Orthopaedic Research

Tập 33 Số 3

373-381

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