Monosodium iodoacetate induces apoptosis via the mitochondrial pathway involving ROS production and caspase activation in rat chondrocytes in vitro.

Liping Jiang, Longjie Li, Chengyan Geng, Dezheng Gong, Lijie Jiang, Nobuyuki Ishikawa, Koji Kajima, Laifu Zhong

China-Japanese Joint Institute for Medical and Pharmaceutical Science, Dalian Medical University, Dalian, China.

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2013 Mar

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Monosodium iodoacetate (MIA) is an inhibitor of glyceraldehyde-3-phosphate dehydrogenase activity, and causes dose-dependent cartilage degradation resembling the pathological changes of human osteoarthritis (OA). In this study, we assessed the apoptosis induced by MIA and clarified the underlying mechanisms using the primary rat chondrocytes. The apoptosis of primary rat chondrocytes was analyzed by flow cytometry. The levels of mitochondrial membrane potential (ΔΨm) were evaluated using fluorescence spectrophotometer. The production of reactive oxygen species (ROS) was determined by fluorescence spectrophotometer. Apoptosis-related protein cytochrome c and procaspase-3 expressions were examined by Western blotting. We found that MIA treatment induces apoptosis in chondrocytes, as confirmed by increases in the percent of apoptotic cells, up-regulation of cytochrome c and caspase-3 protein levels. Treatment with MIA increases ROS production and decreases the levels of ΔΨm. The antioxidant, N-acetylcysteine (NAC), significantly prevented the production of ROS, the reduction of ΔΨm, the release of cytochrome c and the activation of caspase-3. Further, NAC completely protected the cells from MIA-induced apoptosis. Together these observations suggest that the mechanisms of MIA-induced apoptosis are primarily via ROS production and mitochondria-mediated caspase-3 activation in primary rat chondrocytes. Copyright © 2012 Orthopaedic Research Society.

Citation

Liping Jiang, Longjie Li, Chengyan Geng, Dezheng Gong, Lijie Jiang, Nobuyuki Ishikawa, Koji Kajima, Laifu Zhong. Monosodium iodoacetate induces apoptosis via the mitochondrial pathway involving ROS production and caspase activation in rat chondrocytes in vitro. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2013 Mar;31(3):364-9