title: Focal adhesion kinase signaling controls cyclic tensile strain enhanced collagen I-induced osteogenic differentiation of human mesenchymal stem cells.
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.
authors.affiliation: Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180-3596, USA.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Ward
authors.forename: William A
authors.initials: WA
authors.lastname: Williams
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Schapiro
authors.forename: Genevieve L
authors.initials: GL
authors.lastname: Weber
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Christy
authors.forename: Megan
authors.initials: M
authors.lastname: Salt
authors.forename: Robert F
authors.initials: RF
authors.lastname: Klees
authors.forename: Adele
authors.initials: A
authors.lastname: Boskey
authors.forename: George E
authors.initials: GE
authors.lastname: Plopper
mesh_terms: D002113:Calcification, Physiologic; D002454:Cell Differentiation; D024042:Collagen Type I / Q000378:metabolism*; D000939:Epitopes / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D040542:Mechanotransduction, Cellular; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis; D010766:Phosphorylation; D017354:Point Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics; D000076182:Sp7 Transcription Factor; D013718:Tensile Strength; D014157:Transcription Factors / Q000235:genetics
chemical_list: D024042:Collagen Type I; D000939:Epitopes; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012795:Sialoglycoproteins; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D015675:Osteocalcin; D051418:Focal Adhesion Kinase 2; C103547:PTK2B protein, human; D048049:Extracellular Signal-Regulated MAP Kinases