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The mechanosensitive Piezo1 channel is required for bone formation

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 that is...

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Autores principales: Sun, Weijia, Chi, Shaopeng, Li, Yuheng, Ling, Shukuan, Tan, Yingjun, Xu, Youjia, Jiang, Fan, Li, Jianwei, Liu, Caizhi, Zhong, Guohui, Cao, Dengchao, Jin, Xiaoyan, Zhao, Dingsheng, Gao, Xingcheng, Liu, Zizhong, Xiao, Bailong, Li, Yingxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685704/
https://www.ncbi.nlm.nih.gov/pubmed/31290742
http://dx.doi.org/10.7554/eLife.47454
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author Sun, Weijia
Chi, Shaopeng
Li, Yuheng
Ling, Shukuan
Tan, Yingjun
Xu, Youjia
Jiang, Fan
Li, Jianwei
Liu, Caizhi
Zhong, Guohui
Cao, Dengchao
Jin, Xiaoyan
Zhao, Dingsheng
Gao, Xingcheng
Liu, Zizhong
Xiao, Bailong
Li, Yingxian
author_facet Sun, Weijia
Chi, Shaopeng
Li, Yuheng
Ling, Shukuan
Tan, Yingjun
Xu, Youjia
Jiang, Fan
Li, Jianwei
Liu, Caizhi
Zhong, Guohui
Cao, Dengchao
Jin, Xiaoyan
Zhao, Dingsheng
Gao, Xingcheng
Liu, Zizhong
Xiao, Bailong
Li, Yingxian
author_sort Sun, Weijia
collection PubMed
description 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 that is critical for various biological processes, plays a critical role in bone formation. Knockout of Piezo1 in osteoblast lineage cells disrupts the osteogenesis of osteoblasts and severely impairs bone structure and strength. Bone loss that is induced by mechanical unloading is blunted in knockout mice. Intriguingly, simulated microgravity treatment reduced the function of osteoblasts by 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.
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spelling pubmed-66857042019-08-09 The mechanosensitive Piezo1 channel is required for bone formation Sun, Weijia Chi, Shaopeng Li, Yuheng Ling, Shukuan Tan, Yingjun Xu, Youjia Jiang, Fan Li, Jianwei Liu, Caizhi Zhong, Guohui Cao, Dengchao Jin, Xiaoyan Zhao, Dingsheng Gao, Xingcheng Liu, Zizhong Xiao, Bailong Li, Yingxian eLife Cell Biology 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 that is critical for various biological processes, plays a critical role in bone formation. Knockout of Piezo1 in osteoblast lineage cells disrupts the osteogenesis of osteoblasts and severely impairs bone structure and strength. Bone loss that is induced by mechanical unloading is blunted in knockout mice. Intriguingly, simulated microgravity treatment reduced the function of osteoblasts by 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. eLife Sciences Publications, Ltd 2019-07-10 /pmc/articles/PMC6685704/ /pubmed/31290742 http://dx.doi.org/10.7554/eLife.47454 Text en © 2019, Sun et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Sun, Weijia
Chi, Shaopeng
Li, Yuheng
Ling, Shukuan
Tan, Yingjun
Xu, Youjia
Jiang, Fan
Li, Jianwei
Liu, Caizhi
Zhong, Guohui
Cao, Dengchao
Jin, Xiaoyan
Zhao, Dingsheng
Gao, Xingcheng
Liu, Zizhong
Xiao, Bailong
Li, Yingxian
The mechanosensitive Piezo1 channel is required for bone formation
title The mechanosensitive Piezo1 channel is required for bone formation
title_full The mechanosensitive Piezo1 channel is required for bone formation
title_fullStr The mechanosensitive Piezo1 channel is required for bone formation
title_full_unstemmed The mechanosensitive Piezo1 channel is required for bone formation
title_short The mechanosensitive Piezo1 channel is required for bone formation
title_sort mechanosensitive piezo1 channel is required for bone formation
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685704/
https://www.ncbi.nlm.nih.gov/pubmed/31290742
http://dx.doi.org/10.7554/eLife.47454
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