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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.

Keywords

Tensile strain, Osteogenesis, hMSC, FAK, Point Mutagenesis, Collagen-I ECM, Gene Expression, Mineralization

Cite This Article

F., D., Williams, W. A., Schapiro, N. E., Christy, S. R., Weber, G. L. et al. (2007). Focal Adhesion Kinase Signaling Controls Cyclic Tensile Strain Enhanced Collagen I-Induced Osteogenic Differentiation of Human Mesenchymal Stem Cells. Molecular & Cellular Biomechanics, 4(4), 177–188.



This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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