Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition.
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Brunner M, Millon-Fremillon A, Chevalier G, Nakchbandi IA, Mosher D, Block MR, Albiges-Rizo C, Bouvard D
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.
- PubMed ID
- 21768292 [ View in PubMed]
- 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 beta1 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 beta1 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 beta1 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 beta1 integrin-containing fibrillar adhesions and, thereby, regulates fibronectin deposition and osteoblast mineralization.