Open Access

ARTICLE

Focal Adhesion Kinase Signaling Controls Cyclic Tensile Strain Enhanced Collagen I-Induced Osteogenic Differentiation of Human Mesenchymal Stem Cells

Donald F. Ward Jr.^*, William A. Williams^*, Nicole E. Schapiro^*, Samuel R. Christy^*, Genevieve L. Weber^*, Megan Salt, Robert F. Klees^*, Adele Boskey^†, George E. Plopper ^∗,‡

* Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180-3596,USA
† Hospital for Special Surgery, New York City, NY 10021, USA
‡ Corresponding author. Center for Biotechnology and Interdisciplinary Studies, BCHM-2, Rensselaer Polytechnic Institute, 110 8 th St, Troy, NY 12180, Phone: (518) 276-6332, Fax: (518) 276-2851, Email: ploppg@rpi.edu

Molecular & Cellular Biomechanics 2007, 4(4), 177-188. https://doi.org/10.3970/mcb.2007.004.177

Abstract

Focal adhesion kinase (FAK) is a key integrator of integrin-mediated signals from the extracellular matrix to the cytoskeleton and downstream signaling molecules. FAK is activated by phosphorylation at specific tyrosine residues, which then stimulate downstream signaling including the ERK1/2 pathway, leading to a variety of cellular responses. In this study, we examined the effects of FAK point mutations at tyrosine residues (Y397, Y925, Y861, and Y576/7) on osteogenic differentiation of human mesenchymal stem cells exposed to collagen I and cyclic tensile strain. Our results demonstrate that FAK signaling emanating from Y397, Y925, and to a lesser extent Y576/7, but not from Y861, controls osteogenic differentiation through an ERK1/2 pathway, as measured by expression levels of key osteogenesis marker genes and subsequent matrix mineralization. These data indicate that FAK is a critical decision maker in extracellular matrix/strain-enhanced osteogenic differentiation.

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Keywords

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