The mechanosensitive Piezo1 channel is required for bone formation

eLife

  ^{1    1    1    2    2    2    2    2    2    2    2    2    2    2    2    2    3} 

[1] State Key Laboratory of Membrane Biology, Tsinghua-Peking Joint Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Pharmaceutical Sciences, Tsinghua University, Beijing, China;State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, China;The Second Affiliated Hospital of Soochow University, Suzhou, China;

关键词: Piezo1;    mechanosensitive ion channel;    mechanotransduction;    bone formation;    unloading;    osteoblast;    Human;    Mouse;   

DOI  :  10.7554/eLife.47454

来源: publisher

【 摘 要 】

10.7554/eLife.47454.001Mechanical 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.

【 授权许可】

CC BY