Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition

J Cell Biol. 2011 Jul 25;194(2):307-22. doi: 10.1083/jcb.201007108. Epub 2011 Jul 18.

Abstract

The morphogenetic and differentiation events required for bone formation are orchestrated by diffusible and insoluble factors that are localized within the extracellular matrix. In mice, the deletion of ICAP-1, a modulator of β1 integrin activation, leads to severe defects in osteoblast proliferation, differentiation, and mineralization and to a delay in bone formation. Deposition of fibronectin and maturation of fibrillar adhesions, adhesive structures that accompany fibronectin deposition, are impaired upon ICAP-1 loss, as are type I collagen deposition and mineralization. Expression of β1 integrin with a mutated binding site for ICAP-1 recapitulates the ICAP-1-null phenotype. Follow-up experiments demonstrated that ICAP-1 negatively regulates kindlin-2 recruitment onto the β1 integrin cytoplasmic domain, whereas an excess of kindlin-2 binding has a deleterious effect on fibrillar adhesion formation. These results suggest that ICAP-1 works in concert with kindlin-2 to control the dynamics of β1 integrin-containing fibrillar adhesions and, thereby, regulates fibronectin deposition and osteoblast mineralization.

Publication types

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

MeSH terms

  • Animals
  • Calcification, Physiologic*
  • Cell Differentiation
  • Cell Proliferation
  • Cytoskeletal Proteins / metabolism
  • Extracellular Matrix / metabolism
  • Fibronectins / metabolism*
  • Integrin beta1 / metabolism*
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Muscle Proteins / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Protein Binding

Substances

  • Cytoskeletal Proteins
  • Fibronectins
  • ICAP-1 protein, mouse
  • Integrin beta1
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • kindlin-2 protein, mouse