Defective osteoblast function in ICAP-1-deficient mice

Development. 2007 Jul;134(14):2615-25. doi: 10.1242/dev.000877. Epub 2007 Jun 13.

Abstract

The integrin receptor family plays important roles in cell-to-cell and cell-to-extracellular matrix interactions through the recruitment of accessory molecules. One of them, the integrin cytoplasmic domain-associated protein-1 (ICAP-1; also known as ITGB1BP1), specifically interacts with the cytoplasmic domain of the beta1 integrin subunit and negatively regulates its function in vitro. To address the role of ICAP-1 in vivo, we ablated the Icap-1 gene in mice. We report an unexpected role of ICAP-1 in osteoblast function during bone development. Icap-1-deficient mice suffer from reduced osteoblast proliferation and delayed bone mineralization, resulting in the retarded formation of bone sutures. In vitro studies reveal that primary and immortalized Icap-1-null osteoblasts display enhanced adhesion and spreading on extracellular matrix substrates, probably owing to an increase in beta1 integrin activation. Finally, we provide evidence that ICAP-1 promotes differentiation of osteoprogenitors by supporting their condensation through modulating the integrin high affinity state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Development*
  • Calcification, Physiologic
  • Cell Adhesion
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Craniofacial Abnormalities / genetics
  • Dwarfism / genetics
  • Integrin beta1 / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Osteoblasts / cytology
  • Osteoblasts / physiology*
  • Osteogenesis
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Skull / embryology
  • Skull / growth & development
  • Skull / physiology
  • Stem Cells / cytology
  • Stem Cells / physiology

Substances

  • ICAP-1 protein, mouse
  • Integrin beta1
  • Intracellular Signaling Peptides and Proteins
  • Protein Subunits