Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity

Nat Commun. 2020 Jun 23;11(1):3168. doi: 10.1038/s41467-020-16971-6.

Abstract

In humans, mutations in the PIEZO2 gene, which encodes for a mechanosensitive ion channel, were found to result in skeletal abnormalities including scoliosis and hip dysplasia. Here, we show in mice that loss of Piezo2 expression in the proprioceptive system recapitulates several human skeletal abnormalities. While loss of Piezo2 in chondrogenic or osteogenic lineages does not lead to human-like skeletal abnormalities, its loss in proprioceptive neurons leads to spine malalignment and hip dysplasia. To validate the non-autonomous role of proprioception in hip joint morphogenesis, we studied this process in mice mutant for proprioceptive system regulators Runx3 or Egr3. Loss of Runx3 in the peripheral nervous system, but not in skeletal lineages, leads to similar joint abnormalities, as does Egr3 loss of function. These findings expand the range of known regulatory roles of the proprioception system on the skeleton and provide a central component of the underlying molecular mechanism, namely Piezo2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple
  • Animals
  • Bone Remodeling
  • Core Binding Factor Alpha 3 Subunit / metabolism
  • Disease Models, Animal
  • Early Growth Response Protein 3 / metabolism
  • Genetic Predisposition to Disease / genetics
  • Hip Dislocation / genetics
  • Hip Dislocation / metabolism
  • Hip Dislocation / pathology
  • Hip Joint / anatomy & histology
  • Hip Joint / metabolism
  • Hip Joint / pathology
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Musculoskeletal Abnormalities / genetics
  • Musculoskeletal Abnormalities / metabolism*
  • Musculoskeletal Abnormalities / pathology
  • Musculoskeletal System / metabolism*
  • Musculoskeletal System / pathology
  • Neurons / metabolism*
  • Proprioception / physiology*
  • Scoliosis

Substances

  • Core Binding Factor Alpha 3 Subunit
  • Egr3 protein, mouse
  • Ion Channels
  • Piezo2 protein, mouse
  • Runx3 protein, mouse
  • Early Growth Response Protein 3