• Qingshan Yang, Shifang Guo, Song Wang, Yaowen Qian, Huiping Tai, and Zhixin Chen.
• Department of Orthopaedics, Gan Su Province Hospital, Lan Zhou, 73000, China.
• Fundam Clin Pharmacol. 2015 Feb 1; 29 (1): 54-61.

AbstractAdvanced glycation end products (AGEs) are an important mediator in osteoarthritis (OA) and cause apoptosis in articular chondrocytes. Mitochondrial function is involved in modulating apoptosis of articular chondrocytes. This study was performed to investigate the mechanism of AGEs-induced chondrocyte apoptosis. The ratio of apoptotic cell and cell viability was surveyed by TUNEL, MTT,LDH release assay. The reactive oxygen species was determined by the fluorescent probe 2', 7'-dichlorofluorescein diacetate. The expression of caspase-3 and cytochrome c was detected by Western blot. The mitochondrial membrane potential (▵Ψm) was evaluated by rhodamine-123 fluorescence. We found that AGEs induced apoptosis in primary rabbit chondrocytes, upregulation of ROS production, cytochrome c, and caspase-3 levels. Simultaneously, AGEs decreases the levels of ▵Ψm and ATP production; however, the antibody of AGEs (sRAGE) and antioxidant-N-acetylcys-teine (NAC) significantly reversed AGEs-induced the above damage thus to protect the cells from apoptosis. These observations suggested that the mechanism of AGEs-induced chondrocyte apoptosis was primarily via ROS production and mitochondria-mediated caspase-3 activation. © 2014 Société Française de Pharmacologie et de Thérapeutique.

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