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CypD-mPTP axis regulates mitochondrial functions contributing to osteogenic dysfunction of MC3T3-E1 cells in inflammation

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Abstract

Bone is a dynamic organ, the bone-forming osteoblasts and bone-resorbing osteoclasts form the physiological basis of bone remodeling process. During pathological process of numerous inflammatory diseases, these two aspects are uncoupled and the balance is usually tipped in favor of bone destruction. Evidence suggests that the inflammatory destruction of bone is mainly attributed to oxidative stress and is closely related to mitochondrial dysfunction. The mechanisms underlying osteogenic dysfunction in inflammation still need further investigation. Reactive oxygen species (ROS) is associated with mitochondrial dysfunction and cellular damage. Here, we reported an unexplored role of cyclophilin D (CypD), the major modulator of mitochondrial permeability transition pore (mPTP), and the CypD-mPTP axis in inflammation-induced mitochondrial dysfunction and bone damage. And the protective effects of knocking down CypD by siRNA interference or the addition of cyclosporin A (CsA), an inhibitor of CypD, were evidenced by rescued mitochondrial function and osteogenic function of osteoblast under tumor necrosis factor-α (TNF-α) treatment. These findings provide new insights into the role of CypD-mPTP-dependent mitochondrial pathway in the inflammatory bone injury. The protective effect of CsA or other moleculars affecting the mPTP formation may hold promise as a potential novel therapeutic strategy for inflammation-induced bone damage via mitochondrial pathways.

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Funding

This study was sponsored by a grant from the National Key Research and Development Program of China (2016YFC1102704), the National Natural Science Foundation of China (no.81400483), and Sichuan Province Science and Technology Innovation Team Program (2011JTD0006).

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Author notes

  1. Xueqi Gan and Ling Zhang contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Haiyang Yu 14 S Renmin Rd. 3rd Sec., Chengdu, 610041, Sichuan, People’s Republic of China

    Xueqi Gan, Ling Zhang, Beilei Liu, Zhuoli Zhu, Yuting He, Junsheng Chen, Junfei Zhu & Haiyang Yu

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  1. Xueqi Gan
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  2. Ling Zhang
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  3. Beilei Liu
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  6. Junsheng Chen
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Correspondence to Haiyang Yu.

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Gan, X., Zhang, L., Liu, B. et al. CypD-mPTP axis regulates mitochondrial functions contributing to osteogenic dysfunction of MC3T3-E1 cells in inflammation. J Physiol Biochem 74, 395–402 (2018). https://doi.org/10.1007/s13105-018-0627-z

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  • DOI: https://doi.org/10.1007/s13105-018-0627-z

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