Journal
ULTRASOUND IN MEDICINE AND BIOLOGY
Volume 38, Issue 10, Pages 1734-1743Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ultrasmedbio.2012.06.002
Keywords
Chondrocyte; Ultrasound; Mechanotransduction; Integrin; Focal adhesion kinase (FAK); Src; p130 Crk-associated substrate (p130Cas); CrkII; Extracellular-regulated kinase (Erk)
Funding
- American Recovery and Reinvestment Act of research grant from the Department of Health and Human Services [1R21RR024437-01A1]
- State of Nebraska grant Stem Cell
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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. (E-mail: asubramanian2@unl.edu) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology
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