BioProject

osteoblasts and increases bone strength, but the mechanisms are poorly understood. More...

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

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 osteocytes sense and respond to changes in

mechanical load and identify a novel target for anabolic bone therapy. Less...