Influence mechanical signals promotes bone anabolism via Piezo1

Mechanical loading, such as caused by exercise, stimulates bone formation byosteoblasts and increases bone strength, but the mechanisms are poorly understood.Osteocytes reside in bone matrix, sense changes in mechanical load, and producesignals that alter bone formation by osteoblasts. We report that the ion channel Piezo1is required for changes in gene expression induced by fluid shear stress in culturedosteocytes and stimulation of Piezo1 by a small molecule agonist is sufficient toreplicate the effects of fluid flow on osteocytes. Conditional deletion of Piezo1 inosteocytes notably reduced bone mass and strength in mice. Conversely,administration of a Piezo1 agonist to adult mice increased bone mass, mimicking theeffects of mechanical loading. These results demonstrate that Piezo1 is amechanosensitive ion channel by which osteocytes sense and respond to changes inmechanical load and identify a novel target for anabolic bone therapy.