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MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts

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Abstract

The development of postmenopausal osteoporosis is thought to be closely related to oxidative stress. Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase (SOD) mimetic, could protect osteoblasts from cytotoxicity and dysfunction caused by oxidative stress. However, it is still unclear whether MnTBAP has effect on the development of postmenopausal osteoporosis. Here, we demonstrated that MnTBAP can inhibit bone mass loss and bone microarchitecture alteration, and increase the number of osteoblasts while reducing osteoclasts number, as well as improve the BMP-2 expression level in ovariectomized rat model. Additionally, MnTBAP can also prevent oxidative stress status up-regulation induced by ovariotomy and hydrogen peroxide (H2O2). Furthermore, MnTBAP reduced the effect of oxidative stress on osteoblasts differentiation and increased BMP-2 expression levels with a dose-dependent manner, via reducing the levels of mitochondrial oxidative stress in osteoblasts. Taken together, our findings provide new insights that MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts, and maybe a potential drug in postmenopausal osteoporosis therapy.

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Acknowledgements

DSL acknowledges the National Natural Science Foundation of China (Grant No. 81600696).

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Authors and Affiliations

  1. Huangshi Central Hospital (Affiliated Hospital of Hubei Polytechnic University), Edong Healthcare Group, Huangshi, China

    Xiangchang Cao

  2. Department of Orthopaedic Surgery, The Affiliated Southeast Hospital of Xiamen University, Zhangzhou, China

    Deqing Luo, Teng Li, Zunxian Huang, Weitao Zou, Lei Wang, Kejian Lian & Dasheng Lin

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  1. Xiangchang Cao
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  2. Deqing Luo
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  3. Teng Li
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  4. Zunxian Huang
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  7. Kejian Lian
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Contributions

Study design: XCC, KJL and DSL. Study conduct: XCC, DQL, TL, ZXH, WTZ and LW. Data analysis: XCC, DQL, TL. Drafting manuscript: XCC and DSL. Approving final version of manuscript: XCC, KJL and DSL. DSL takes responsibility for the integrity of the data analysis.

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Correspondence to Kejian Lian or Dasheng Lin.

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All procedures were approved by the Animal Care and Use Committee at Xiamen University.

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Cao, X., Luo, D., Li, T. et al. MnTBAP inhibits bone loss in ovariectomized rats by reducing mitochondrial oxidative stress in osteoblasts. J Bone Miner Metab 38, 27–37 (2020). https://doi.org/10.1007/s00774-019-01038-4

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