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Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening

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Abstract

Existing evidences have emphasized an important role of oxidative stress in dexamethasone (Dex)-induced osteoblastic cell damages. Here, we investigated the possible anti-Dex activity of edaravone in osteoblastic cells, and studied the underlying mechanisms. We showed that edaravone dose-dependently attenuated Dex-induced death and apoptosis of established human or murine osteoblastic cells. Further, Dex-mediated damages to primary murine osteoblasts were also alleviated by edaravone. In osteoblastic cells/osteoblasts, Dex induced significant oxidative stresses, tested by increased levels of reactive oxygen species and lipid peroxidation, which were remarkably inhibited by edaravone. Meanwhile, edaravone repressed Dex-induced mitochondrial permeability transition pore (mPTP) opening, or mitochondrial membrane potential reduction, in osteoblastic cells/osteoblasts. Significantly, edaravone-induced osteoblast-protective activity against Dex was alleviated with mPTP inhibition through cyclosporin A or cyclophilin-D siRNA. Together, we demonstrate that edaravone protects osteoblasts from Dex-induced damages probably through inhibiting oxidative stresses and following mPTP opening.

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Acknowledgments

This study is supported by the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, Wuhan, China

    Wen-xiao Sun

  2. Department of Clinical Laboratory, The People’s Hospital of Lishui, Lishui, 323000, Zhejiang, China

    Hai-ya Zheng

  3. Department of Orthopaedics, The People’s Hospital of Lishui, Lishui, 323000, Zhejiang, China

    Jun Lan

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  1. Wen-xiao Sun
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  2. Hai-ya Zheng
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  3. Jun Lan
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Correspondence to Jun Lan.

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Sun, Wx., Zheng, Hy. & Lan, J. Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening. Mol Cell Biochem 409, 51–58 (2015). https://doi.org/10.1007/s11010-015-2511-2

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  • DOI: https://doi.org/10.1007/s11010-015-2511-2

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