Integrin-mediated mechanotransduction pathway of low-intensity continuous ultrasound in human chondrocytes

Authors

Nicholas P. Whitney, University of Nebraska - Lincoln
Allyson C. Lamb, University of Nebraska-Lincoln
Tobias M. Louw, University of Nebraska-Lincoln
Anuradha Subramanian, University of Nebraska-LincolnFollow

Date of this Version

2012

Document Type

Article

Citation

Ultrasound Med Biol. 2012 October ; 38(10): 1734–1743.

Comments

Copyright 2012 Whitney et al.

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.