Defective osteoblast function in ICAP-1-deficient mice
Defective osteoblast function in ICAP-1-deficient mice
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DOI：
10.1242/dev.000877
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发表时间：
2007-07-15
期刊：
影响因子：
4.6
通讯作者：
Faessler, Reinhard
中科院分区：
文献类型：
--
作者：
Bouvard, Daniel;Aszodi, Attila;Faessler, Reinhard
整合素受体家族通过募集辅助分子在细胞与细胞和细胞与细胞外基质的相互作用中起重要作用。其中之一，整合素胞质结构域相关蛋白-1（ICAP-1;也称为ITGB 1BP 1），特异性地与β 1整合素亚基的胞质结构域相互作用并在体外负调节其功能。为了阐明ICAP-1在体内的作用，我们在小鼠中切除了Icap-1基因。我们报告了ICAP-1在骨发育成骨细胞功能中的一个意想不到的作用。Icap-1缺陷小鼠患有成骨细胞增殖减少和骨矿化延迟，导致骨缝形成延迟。体外研究表明，原代和永生化的Icap-1 null成骨细胞在细胞外基质基质上显示出增强的粘附和铺展，这可能是由于β 1整合素活化的增加。最后，我们提供的证据表明，ICAP-1促进骨祖细胞的分化，通过调节整合素的高亲和力状态，支持他们的凝聚。
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 beta 1 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-1null osteoblasts display enhanced adhesion and spreading on extracellular matrix substrates, probably owing to an increase in beta 1 integrin activation. Finally, we provide evidence that ICAP-1 promotes differentiation of osteoprogenitors by supporting their condensation through modulating the integrin high affinity state.