Integrin αv in the Mechanical Response of Osteoblast Lineage Cells

Biochem Biophys Res Commun. 2014 May 2;447(2):352-7. doi: 10.1016/j.bbrc.2014.04.006. Epub 2014 Apr 13.

Abstract

Although osteoblast lineage cells, especially osteocytes, are thought to be a primary mechanosensory cell in bone, the identity of the mechano-receptor and downstream mechano-signaling pathways remain largely unknown. Here we show using osteoblastic cell model of mechanical stimulation with fluid shear stress that in the absence of integrin αv, phosphorylation of the Src substrate p130Cas and JNK was impaired, culminating in an inhibition of nuclear translocation of YAP/TAZ and subsequent transcriptional activation of target genes. Targeted deletion of the integrin αv in osteoblast lineage cells results in an attenuated response to mechanical loading in terms of Sost gene expression, indicative of a role for integrin αv in mechanoreception in vivo. Thus, integrin αv may be integral to a mechanosensing machinery in osteoblastic cells and involved in activation of a Src-JNK-YAP/TAZ pathway in response to mechanical stimulation.

Keywords: Integrin αv; Mechanotransduction; Osteoblast; YAP/TAZ; p130Cas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Cycle Proteins
  • Cell Lineage
  • Cells, Cultured
  • Integrin alphaV / genetics
  • Integrin alphaV / physiology*
  • MAP Kinase Kinase 4 / metabolism
  • Mechanotransduction, Cellular / genetics
  • Mechanotransduction, Cellular / physiology*
  • Mice
  • Osteoblasts / physiology*
  • Phosphoproteins / metabolism
  • Shear Strength / physiology*
  • Stress, Mechanical*
  • Transcription Factors / metabolism
  • src-Family Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Integrin alphaV
  • Phosphoproteins
  • Taz protein, mouse
  • Transcription Factors
  • Yap protein, mouse
  • src-Family Kinases
  • MAP Kinase Kinase 4