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Cell apoptosis induced by zinc deficiency in osteoblastic MC3T3-E1 cells via a mitochondrial-mediated pathway

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Abstract

Deficiency of zinc plays an important role in the pathogenesis of osteoporosis; however, the underlying mechanism is not well understood. Apoptosis of osteoblast causing the loss of bone mass is an important event in the osteoporosis. In this article, we investigated whether zinc deficiency would induce cell apoptosis in MC3T3-E1 cells and ask if it is involved in mitochondrial-mediated pathway. Significant increased apoptosis were observed in zinc deficiency group (ZnD: 5 μM TPEN and 1 μM zinc) compared with untreated control or zinc adequacy group (ZnA: 5 μM TPEN and 15 μM zinc). The mitochondrial membrane potential was strikingly reduced in ZnD group. Furthermore, we observed that the levels of Bax in mitochondria fraction and cyto c, AIF, and cleaved caspase-3/-9 in cytosol fraction were increased in ZnD group. We proposed that zinc deficiency would induce the translocation of Bax into mitochondria, which could lead to the reduction in mitochondrial membrane potential as well as the increase in mitochondrial membrane permeability. In addition, cyto c and AIF were released from mitochondria into the cytosol, which finally activated caspase-dependent and caspase-independent apoptosis processes in MC3T3-E1 cells. Our findings suggested that zinc deficiency is capable of inducing apoptosis through a mitochondria-mediated pathway in osteoblastic cells.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 30771813) and the Natural Science Foundation of Liaoning Province.

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Authors and Affiliations

  1. Department of Orthopedics, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, People’s Republic of China

    Baolei Guo, Maowei Yang, Dan Liang, Lei Yang, Junjun Cao & Le Zhang

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  1. Baolei Guo
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  2. Maowei Yang
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  3. Dan Liang
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  4. Lei Yang
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  5. Junjun Cao
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  6. Le Zhang
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Correspondence to Maowei Yang.

Additional information

Baolei Guo and Maowei Yang contributed equally to this study.

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Guo, B., Yang, M., Liang, D. et al. Cell apoptosis induced by zinc deficiency in osteoblastic MC3T3-E1 cells via a mitochondrial-mediated pathway. Mol Cell Biochem 361, 209–216 (2012). https://doi.org/10.1007/s11010-011-1105-x

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  • DOI: https://doi.org/10.1007/s11010-011-1105-x

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