Focal adhesion kinase signaling controls cyclic tensile strain enhanced collagen I-induced osteogenic differentiation of human mesenchymal stem cells

Mol Cell Biomech. 2007 Dec;4(4):177-88.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcification, Physiologic
  • Cell Differentiation*
  • Collagen Type I / metabolism*
  • Epitopes / immunology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Focal Adhesion Kinase 2 / genetics*
  • Focal Adhesion Kinase 2 / metabolism*
  • Humans
  • Integrin-Binding Sialoprotein
  • Mechanotransduction, Cellular*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Osteocalcin / genetics
  • Osteogenesis*
  • Phosphorylation
  • Point Mutation
  • Proto-Oncogene Proteins c-myc / genetics
  • Retroviridae / genetics
  • Sialoglycoproteins / genetics
  • Sp7 Transcription Factor
  • Tensile Strength
  • Transcription Factors / genetics

Substances

  • Collagen Type I
  • Epitopes
  • IBSP protein, human
  • Integrin-Binding Sialoprotein
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • Sialoglycoproteins
  • Sp7 Transcription Factor
  • SP7 protein, human
  • Transcription Factors
  • Osteocalcin
  • Focal Adhesion Kinase 2
  • PTK2B protein, human
  • Extracellular Signal-Regulated MAP Kinases