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The mechanosensitive Piezo1 channel is required for bone formation

  1. Weijia Sun
  2. Shaopeng Chi
  3. Yuheng Li
  4. Shukuan Ling
  5. Yingjun Tan
  6. Youjia Xu
  7. Fan Jiang
  8. Jianwei Li
  9. Caizhi Liu
  10. Guohui Zhong
  11. Dengchao Cao
  12. Xiaoyan Jin
  13. Dingsheng Zhao
  14. Xingcheng Gao
  15. Zizhong Liu
  16. Bailong Xiao  Is a corresponding author
  17. Yingxian Li  Is a corresponding author
  1. China Astronaut Research and Training Center, China
  2. Tsinghua University, China
  3. Soochow University, China
Research Article
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Cite this article as: eLife 2019;8:e47454 doi: 10.7554/eLife.47454

Abstract

Mechanical load of the skeleton system is essential for the development, growth, and maintenance of bone. However, the molecular mechanism by which mechanical stimuli are converted into osteogenesis and bone formation remains unclear. Here we report that Piezo1, a bona fide mechanotransducer critical for various biological processes, plays a critical role in bone formation. Knockout of Piezo1 in osteoblast lineage cells disrupts osteogenesis of osteoblasts and severely impairs bone structure and strength. Mechanical unloading induced bone loss is blunted in the Piezo1 knockout mice. Intriguingly, simulated microgravity treatment reduced the function of osteoblasts via suppressing the expression of Piezo1. Furthermore, osteoporosis patients show reduced expression of Piezo1, which is closely correlated with osteoblast dysfunction. These data collectively suggest that Piezo1 functions as a key mechanotransducer for conferring mechanosensitivity to osteoblasts and determining mechanical-load-dependent bone formation, and represents a novel therapeutic target for treating osteoporosis or mechanical unloading-induced severe bone loss.

Article and author information

Author details

  1. Weijia Sun

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Shaopeng Chi

    State Key Laboratory of Membrane Biology, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yuheng Li

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Shukuan Ling

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yingjun Tan

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Youjia Xu

    The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Fan Jiang

    State Key Laboratory of Membrane Biology, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Jianwei Li

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Caizhi Liu

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Guohui Zhong

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Dengchao Cao

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Xiaoyan Jin

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Dingsheng Zhao

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Xingcheng Gao

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Zizhong Liu

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  16. Bailong Xiao

    State Key Laboratory of Membrane Biology, Tsinghua University, Beijing, China
    For correspondence
    xbailong@mail.tsinghua.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  17. Yingxian Li

    State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China
    For correspondence
    yingxianli@aliyun.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5440-3281

Funding

National Natural Science Foundation of China (31630038)

  • Yingxian Li

National Natural Science Foundation of China (81822026)

  • Shukuan Ling

National Natural Science Foundation of China (91740114)

  • Yingxian Li

National Natural Science Foundation of China (81830061)

  • Yingxian Li

National Natural Science Foundation of China (31700741)

  • Yuheng Li

National Natural Science Foundation of China (31825014)

  • Bailong Xiao

National Natural Science Foundation of China (31630090)

  • Bailong Xiao

Ministry of Science and Technology of the People's Republic of China (2016YFA0500402)

  • Bailong Xiao

Ministry of Science and Technology of the People's Republic of China (2015CB910102)

  • Bailong Xiao

National Natural Science Foundation of China (31800994)

  • Weijia Sun

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal studies were performed according to approved guidelines for the use and care of live animals (Guideline on Administration of Laboratory Animals released in1988 and 2006 Guideline on Humane Treatment of Laboratory Animals from China). All the experimental procedures were approved by the Committees of Animal Ethics and Experimental Safety of China Astronaut Research and Training Center (Reference number: ACC-IACUC-2017-003).

Human subjects: The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki. All the clinical procedures were approved by the Committees of Clinical Ethics in the Second Affiliated Hospital of Soochow University (Reference number: 2016-K-22).

Reviewing Editor

  1. Clifford J Rosen, Maine Medical Center Research Institute, United States

Publication history

  1. Received: April 5, 2019
  2. Accepted: July 6, 2019
  3. Accepted Manuscript published: July 10, 2019 (version 1)

Copyright

© 2019, Sun et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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