Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption

Tanya Dossa, Alice Arabian, Jolene J. Windle, Shoukat Dedhar, Steven L. Teitelbaum, F. Patrick Ross, G. David Roodman, René St-Arnaud

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Bone resorption requires the adhesion of osteoclasts to extracellular matrix (ECM) components, a process mediated by the αvβ 3 integrin. Following engagement with the ECM, integrin receptors signal via multiple downstream effectors, including the integrin-linked kinase (ILK). In order to characterize the physiological role of ILK in bone resorption, we generated mice with an osteoclast-specific Ilk gene ablation by mating mice with a floxed Ilk allele with TRAP-Cre transgenic mice. The TRAP-Cre mice specifically excised floxed alleles in osteoclasts, as revealed by crossing them with the ROSA26R reporter strain. Osteoclast-specific Ilk mutant mice appeared phenotypically normal, but histomorphometric analysis of the proximal tibia revealed an increase in bone volume and trabecular thickness. Osteoclast-specific Ilk ablation was associated with an increase in osteoclastogenesis both in vitro and in vivo. However, the mutant osteoclasts displayed a decrease in resorption activity as assessed by reduced pit formation on dentin slices in vitro and decreased serum concentrations of the C-terminal telopeptide of collagen in vivo. Interestingly, compound heterozygous mice in which one allele of Ilk and one allele of the β3 integrin gene were inactivated (ILK+/-; β3+/-) also had increased trabecular thickness, confirming that β3 integrin and Ilk form part of the same genetic cascade. Our results show that ILK is important for the function, but not the differentiation, of osteoclasts.

Original languageEnglish (US)
Pages (from-to)960-967
Number of pages8
JournalJournal of Cellular Biochemistry
Volume110
Issue number4
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Keywords

  • Integrin-linked kinase
  • Integrins
  • Osteoclast

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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