Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption
✍ Scribed by Tanya Dossa; Alice Arabian; Jolene J. Windle; Shoukat Dedhar; Steven L. Teitelbaum; F. Patrick Ross; G. David Roodman; René St-Arnaud
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 914 KB
- Volume
- 110
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Abstract
Bone resorption requires the adhesion of osteoclasts to extracellular matrix (ECM) components, a process mediated by the α~v~β~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 β~3~ integrin gene were inactivated (ILK^+/−^; β) also had increased trabecular thickness, confirming that β~3~ 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. J. Cell. Biochem. 110: 960–967, 2010. © 2010 Wiley‐Liss, Inc.