Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition. - Archive ouverte HAL Access content directly
Journal Articles Journal of Cell Biology Year : 2011

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

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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.
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Dates and versions

inserm-00610020 , version 1 (20-07-2011)

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Molly Brunner, Angélique Millon-Frémillon, Genevieve Chevalier, Inaam A. Nakchbandi, Deane Mosher, et al.. Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition.. Journal of Cell Biology, 2011, 194 (2), pp.307-22. ⟨10.1083/jcb.201007108⟩. ⟨inserm-00610020⟩
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