The mechanosensitive Piezo1 channel is required for bone formation
- China Astronaut Research and Training Center, China
- Tsinghua University, China
- Soochow University, China
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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.
Reviewing Editor
- Clifford J Rosen, Maine Medical Center Research Institute, United States
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).
Version history
- Received: April 5, 2019
- Accepted: July 6, 2019
- Accepted Manuscript published: July 10, 2019 (version 1)
- 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.
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The mechanosensitive Piezo1 channel is required for bone formation
eLife 8:e47454.
https://doi.org/10.7554/eLife.47454
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