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Article type: Research Article
Authors: Morgan, Jessica M. | Wong, Alice | Genetos, Damian C. | Yellowley, Clare E.
Affiliations: Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA, USA
Note: [] Address for correspondence: Dr. Clare E. Yellowley, Department of Anatomy, Physiology and Cell Biology School of Veterinary Medicine, University of California Davis 4206 VM3A, 1285 Veterinary Medicine Drive, Davis, CA 95616, USA. Tel.: +1 530 754 6513; Fax: +1 530 754 0150; E-mail: [email protected].
Abstract: The ability of bone cells to detect and transduce mechanical signals is central to the mechanism whereby bone adapts to mechanical load and maintains healthy bone mass. Src, a non-receptor tyrosine kinase, is located in focal adhesions, highly specialized and localized sites of attachment, that are thought to be a primary site of mechanotransduction. While Src is activated by mechanical loads in other cell types, its role in osteoblast mechanotransduction is unclear. In this study we examined whether oscillatory fluid flow influenced Src phosphorylation, and Src's role in the flow-induced osteopontin response. Additionally, we investigated the effect of constitutively active Src on osteopontin expression. Oscillatory fluid flow induced a statistically significant increase in phosphorylation of Src at tyrosine residue 416 after a 15 min exposure. Transfection with constitutively-active Src resulted in an increase in Src-Y416 phosphorylation and an increase in osteopontin mRNA transcript under static conditions. However, inhibition of Src activity had no effect on oscillatory fluid flow-stimulated osteopontin expression or ERK1/2 phosphorylation. These data suggest that although Src activity regulates osteopontin expression under static conditions, and is induced under conditions of shear stress, it is not required for load-induced osteopontin expression.
Keywords: Mechanotransduction, oscillatory fluid flow, bone, ERK, fluid shear stress
DOI: 10.3233/BIR-2011-0582
Journal: Biorheology, vol. 48, no. 1, pp. 65-74, 2011
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