@article{f2f1d1c10d2e46d396ecb31ef57c0247,
title = "Stimulation of piezo1 by mechanical signals promotes bone anabolism",
abstract = "Mechanical loading, such as caused by exercise, stimulates bone formation by osteoblasts and increases bone strength, but the mechanisms are poorly understood. Osteocytes reside in bone matrix, sense changes in mechanical load, and produce signals that alter bone formation by osteoblasts. We report that the ion channel Piezo1 is required for changes in gene expression induced by fluid shear stress in cultured osteocytes and stimulation of Piezo1 by a small molecule agonist is sufficient to replicate the effects of fluid flow on osteocytes. Conditional deletion of Piezo1 in osteoblasts and osteocytes notably reduced bone mass and strength in mice. Conversely, administration of a Piezo1 agonist to adult mice increased bone mass, mimicking the effects of mechanical loading. These results demonstrate that Piezo1 is a mechanosensitive ion channel by which osteoblast lineage cells sense and respond to changes in mechanical load and identify a novel target for anabolic bone therapy.",
author = "Xuehua Li and Li Han and Intawat Nookaew and Erin Mannen and Silva, {Matthew J.} and Maria Almeida and Jinhu Xiong",
note = "Funding Information: We thank CA O?Brien for valuable discussions and advice; IB Gubrij, J Kordsmeier, JA Crawford, RD Peek, SB Berryhill, WR Hogue and JJ Goellner for technical support; AG Robling (Indiana University School of Medicine) for the tibia cross sectioning protocol, the CTPR Developmental Genomics Core, the UAMS Digital Microscopy Core, and the staff of the UAMS Department of Laboratory Animal Medicine. This work was supported by the National Institute of General Medical Sciences (NIGMS) grants P20GM125503 and P20GM121293; the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants R01AR56679 and R01AR047867; and the UAMS Bone and Joint Initiative. Funding Information: We thank CA O{\textquoteright}Brien for valuable discussions and advice; IB Gubrij, J Kordsmeier, JA Crawford, RD Peek, SB Berryhill, WR Hogue and JJ Goellner for technical support; AG Robling (Indiana University School of Medicine) for the tibia cross sectioning protocol, the CTPR Developmental Genomics Core, the UAMS Digital Microscopy Core, and the staff of the UAMS Department of Laboratory Animal Medicine. This work was supported by the National Institute of General Medical Sciences (NIGMS) grants P20GM125503 and P20GM121293; the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants R01AR56679 and R01AR047867; and the UAMS Bone and Joint Initiative. Publisher Copyright: {\textcopyright} Li et al.",
year = "2019",
month = oct,
doi = "10.7554/eLife.49631",
language = "English",
volume = "8",
journal = "eLife",
issn = "2050-084X",
}