靶向miR-337可减轻废用性骨质流失。

IF 12.5 1区 生物学 Q1 CELL BIOLOGY
Jiao Li, Ding Ma, Chunxue Zhang, Xueling Zheng, Ruihan Hao, Bin Zuo, Fei Xiao, Yang Li, Yuhang Liu, Zhouyi Duan, Yao Xiong, Orion R Fan, Wenmin Zhu, Liming Dai, Bingjun Zhang, Yi Eve Sun, Xiaoling Zhang
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引用次数: 0

摘要

废弃引起的骨质流失发生在长期卧床不起的病人和太空飞行中的宇航员身上。人们对其潜在机制知之甚少。在废用性骨质流失(称为后肢脱落(HU))的啮齿动物模型中,我们观察到成人骨髓中瘦素受体(LepR)阳性间充质干细胞(MSCs)数量的减少有助于骨质流失。HU后,MicroRNA-337-3p (miR-337)在MSCs中表达上调,通过直接靶向IRS-1抑制PI3kinase-Akt-mTOR通路抑制MSC增殖。Piezo1是感知机械应力的上游受体,通过Hippo-YAP信号通路调控miR-337。值得注意的是,敲除miR-337可通过增加骨髓间充质干细胞增殖和成骨,显著减轻hu诱导的骨丢失,而不是卵巢切除术诱导的骨丢失。最后,将miR-337-/- MSCs移植到野生型HU小鼠中足以减轻骨质流失。这些发现揭示了废用性骨质流失的细胞和分子机制,并强调了一种可行的治疗策略,以防止在地球和太空飞行中废用性或微重力诱导的骨质流失。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting miR-337 mitigates disuse-induced bone loss.

Disuse-induced bone loss occurs in long-term bed-ridden patients and in astronauts during spaceflight. The underlying mechanisms are poorly understood. In a rodent model of disuse-induced bone loss (called hindlimb unloading (HU)), we observed that decreased numbers of leptin receptor (LepR) positive mesenchymal stem cells (MSCs) in adult bone marrow, contribute to bone loss. MicroRNA-337-3p (miR-337) was upregulated in MSCs upon HU and inhibited MSC proliferation by directly targeting IRS-1 to suppress the PI3kinase-Akt-mTOR pathway. Piezo1 was the upstream receptor for sensing mechanical stress and regulated miR-337 through the Hippo-YAP signaling pathway. Remarkably, the knockout of miR-337 significantly attenuated HU-induced, but not ovariectomy-induced, bone loss by increasing MSC proliferation and osteogenesis. Finally, the transplantation of miR-337-/- MSCs into wild-type HU mice was sufficient to mitigate bone loss. These findings reveal the cellular and molecular mechanisms underlying disuse-induced bone loss and highlight a feasible therapeutic strategy to prevent disuse- or microgravity-induced bone loss on Earth and during spaceflight.

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来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
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