Focal adhesion kinase signaling controls cyclic tensile strain enhanced collagen I-induced osteogenic differentiation of human mesenchymal stem cells.
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.
Ward
Donald F
DF
Department of Biology, Rensselaer Polytechnic Institute, Troy, NY 12180-3596, USA.
Williams
William A
WA
Schapiro
Nicole E
NE
Weber
Genevieve L
GL
Christy
Samuel R
SR
Salt
Megan
M
Klees
Robert F
RF
Boskey
Adele
A
Plopper
George E
GE
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
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