title: Advanced glycation end products-induced chondrocyte apoptosis through mitochondrial dysfunction in cultured rabbit chondrocyte.
abstract: Advanced 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.
authors.affiliation: Department of Orthopaedics, Gan Su Province Hospital, Lan Zhou, 73000, China.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Yang
authors.forename: Shifang
authors.initials: S
authors.lastname: Guo
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.forename: Yaowen
authors.initials: Y
authors.lastname: Qian
authors.forename: Huiping
authors.initials: H
authors.lastname: Tai
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D053148:Caspase 3
keywords: advanced glycation end products; apoptosis; chondrocyte; mitochondrial dysfunction; oxidative stress