1. Cell Biology
Download icon

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
  • Cited 29
  • Views 5,375
  • Annotations
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)
  4. Version of Record published: August 7, 2019 (version 2)

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.

Metrics

  • 5,375
    Page views
  • 1,015
    Downloads
  • 29
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Cancer Biology
    2. Cell Biology
    Shima Ghoroghi et al.
    Research Article Updated

    Cancer extracellular vesicles (EVs) shuttle at distance and fertilize pre-metastatic niches facilitating subsequent seeding by tumor cells. However, the link between EV secretion mechanisms and their capacity to form pre-metastatic niches remains obscure. Using mouse models, we show that GTPases of the Ral family control, through the phospholipase D1, multi-vesicular bodies homeostasis and tune the biogenesis and secretion of pro-metastatic EVs. Importantly, EVs from RalA or RalB depleted cells have limited organotropic capacities in vivoand are less efficient in promoting metastasis. RalA and RalB reduce the EV levels of the adhesion molecule MCAM/CD146, which favors EV-mediated metastasis by allowing EVs targeting to the lungs. Finally, RalA, RalB, and MCAM/CD146, are factors of poor prognosis in breast cancer patients. Altogether, our study identifies RalGTPases as central molecules linking the mechanisms of EVs secretion and cargo loading to their capacity to disseminate and induce pre-metastatic niches in a CD146-dependent manner.

    1. Cell Biology
    Mihaela Jagrić et al.
    Research Article

    During metaphase, chromosome position at the spindle equator is regulated by the forces exerted by kinetochore microtubules and polar ejection forces. However, the role of forces arising from mechanical coupling of sister kinetochore fibers with bridging fibers in chromosome alignment is unknown. Here we develop an optogenetic approach for acute removal of PRC1 to partially disassemble bridging fibers and show that they promote chromosome alignment. Tracking of the plus-end protein EB3 revealed longer antiparallel overlaps of bridging microtubules upon PRC1 removal, which was accompanied by misaligned and lagging kinetochores. Kif4A/kinesin-4 and Kif18A/kinesin-8 were found within the bridging fiber and largely lost upon PRC1 removal, suggesting that these proteins regulate the overlap length of bridging microtubules. We propose that PRC1-mediated crosslinking of bridging microtubules and recruitment of kinesins to the bridging fiber promotes chromosome alignment by overlap length-dependent forces transmitted to the associated kinetochore fibers.