Integrin-Mediated Mechanotransduction Pathway of Low-Intensity Continuous Ultrasound in Human Chondrocytes

Nicholas P. Whitney, Allyson C. Lamb, Tobias M. Louw, Anuradha Subramanian

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Chondrocytes are mechanosensitive cells that require mechanical stimulation for proper growth and function in in vitro culture systems. Ultrasound (US) has emerged as a technique to deliver mechanical stress; however, the intracellular signaling components of the mechanotransduction pathways that transmit the extracellular mechanical stimulus to gene regulatory mechanisms are not fully defined. We evaluated a possible integrin/mitogen-activated protein kinase (MAPK) mechanotransduction pathway using Western blotting with antibodies targeting specific phosphorylation sites on intracellular signaling proteins. US stimulation of chondrocytes induced phosphorylation of focal adhesion kinase (FAK), Src, p130 Crk-associated substrate (p130Cas), CrkII and extracellular-regulated kinase (Erk). Furthermore, pre-incubation with inhibitors of integrin receptors, Src and MAPK/Erk kinase (MEK) reduced US-induced Erk phosphorylation levels, indicating integrins and Src are upstream of Erk in an US-mediated mechanotransduction pathway. These findings suggest US signals through integrin receptors to the MAPK/Erk pathway via a mechanotransduction pathway involving FAK, Src, p130Cas and CrkII.

Original languageEnglish (US)
Pages (from-to)1734-1743
Number of pages10
JournalUltrasound in Medicine and Biology
Volume38
Issue number10
DOIs
StatePublished - Oct 2012

Keywords

  • Chondrocyte
  • CrkII
  • Extracellular-regulated kinase (Erk)
  • Focal adhesion kinase (FAK)
  • Integrin
  • Mechanotransduction
  • P130 Crk-associated substrate (p130Cas)
  • Src
  • Ultrasound

ASJC Scopus subject areas

  • Biophysics
  • Radiological and Ultrasound Technology
  • Acoustics and Ultrasonics

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