Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway
Apelin-13 induces mitophagy in bone marrow mesenchymal stem cells to suppress intracellular oxidative stress and ameliorate osteoporosis by activation of AMPK signaling pathway
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Apelin-13通过激活AMPK信号通路诱导骨髓间充质干细胞线粒体自噬抑制细胞内氧化应激并改善骨质疏松
DOI：
10.1016/j.freeradbiomed.2020.12.235
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发表时间：
2021-01-02
影响因子：
7.4
通讯作者：
Yang, Lei
中科院分区：
文献类型：
--
作者：
Chen, Liang;Shi, Xiang;Yang, Lei
骨质疏松症的特征是骨代谢受损。目前的估计表明，它影响到全世界数百万人，并造成严重的社会经济负担。线粒体自噬在骨髓间充质干细胞（BMSCs）成骨分化、矿化和存活中起关键作用。爱帕琳是一种内源性脂肪因子，参与骨稳态。本研究旨在确定Apelin在骨质疏松症过程中的作用，以及它是否影响体外和体内骨质疏松症模型中BMSCs的线粒体自噬、存活和成骨能力。我们的研究结果表明，Apelin在卵巢切除诱导的骨质疏松大鼠中下调，Apelin-13治疗激活BMSC中的线粒体自噬，改善氧化应激，从而通过AMPK-α磷酸化恢复成骨功能。此外，Apelin-13给药恢复了OVX大鼠的骨量和微观结构以及恢复了线粒体自噬，增强了成骨功能。总的来说，我们的研究结果揭示了BMSC中Apelin-13调节的内在机制及其在骨质疏松症治疗中的潜在治疗价值。
Osteoporosis is characterized by impaired bone metabolism. Current estimates show that it affects millions of people worldwide and causes a serious socioeconomic burden. Mitophagy plays key roles in bone marrow mesenchymal stem cells (BMSCs) osteoblastic differentiation, mineralization, and survival. Apelin is an endogenous adipokine that participates in bone homeostasis. This study was performed to determine the role of Apelin in the osteoporosis process and whether it affects mitophagy, survival, and osteogenic capacity of BMSCs in in vitro and in vivo models of osteoporosis. Our results demonstrated that Apelin was down-regulated in ovariectomized-induced osteoporosis rats and Apelin-13 treatment activated mitophagy in BMSCs, ameliorating oxidative stress and thereby reviving osteogenic function via AMPK-alpha phosphorylation. Besides, Apelin-13 administration restored bone mass and microstructure as well as reinstated mitophagy, enhanced osteogenic function in OVX rats. Collectively, our findings reveal the intrinsic mechanisms underlying Apelin-13 regulation in BMSCs and its potential therapeutic values in the treatment of osteoporosis.