TY - EJOU AU - Jr., Donald F. Ward AU - Williams, William A. AU - Schapiro, Nicole E. AU - Christy, Samuel R. AU - Weber, Genevieve L. AU - Klees, Megan Salt, Robert F. AU - Boskey, Adele AU - Plopper, George E. TI - Focal Adhesion Kinase Signaling Controls Cyclic Tensile Strain Enhanced Collagen I-Induced Osteogenic Differentiation of Human Mesenchymal Stem Cells T2 - Molecular \& Cellular Biomechanics PY - 2007 VL - 4 IS - 4 SN - 1556-5300 AB - 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. KW - Tensile strain KW - Osteogenesis KW - hMSC KW - FAK KW - Point Mutagenesis KW - Collagen-I ECM KW - Gene Expression KW - Mineralization DO - 10.3970/mcb.2007.004.177