Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk

Nat Commun. 2020 Jan 15;11(1):282. doi: 10.1038/s41467-019-14146-6.


Wolff's law and the Utah Paradigm of skeletal physiology state that bone architecture adapts to mechanical loads. These models predict the existence of a mechanostat that links strain induced by mechanical forces to skeletal remodeling. However, how the mechanostat influences bone remodeling remains elusive. Here, we find that Piezo1 deficiency in osteoblastic cells leads to loss of bone mass and spontaneous fractures with increased bone resorption. Furthermore, Piezo1-deficient mice are resistant to further bone loss and bone resorption induced by hind limb unloading, demonstrating that PIEZO1 can affect osteoblast-osteoclast crosstalk in response to mechanical forces. At the mechanistic level, in response to mechanical loads, PIEZO1 in osteoblastic cells controls the YAP-dependent expression of type II and IX collagens. In turn, these collagen isoforms regulate osteoclast differentiation. Taken together, our data identify PIEZO1 as the major skeletal mechanosensor that tunes bone homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Resorption / genetics
  • Bone Resorption / pathology*
  • Cell Differentiation
  • Collagen Type II / metabolism
  • Collagen Type IX / metabolism
  • Female
  • Fractures, Bone / genetics
  • Fractures, Bone / pathology
  • Hindlimb Suspension
  • Homeostasis
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Male
  • Mice, Knockout
  • Osteoblasts / metabolism*
  • Osteoclasts / cytology
  • Osteoclasts / metabolism*
  • Osteoporosis / genetics
  • Stress, Mechanical


  • Col2a1 protein, mouse
  • Collagen Type II
  • Collagen Type IX
  • Ion Channels
  • Piezo1 protein, mouse