Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts.

Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts.
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DOI:
10.1016/j.actbio.2013.10.010
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发表时间:
2014-01
期刊:
影响因子:
9.7
通讯作者:
Gower, Laurie B.
Gower, Laurie B.
中科院分区:
工程技术1区
文献类型:
--
作者:
Rodriguez, Douglas E.;Thula-Mata, Taili;Toro, Edgardo J.;Yeh, Ya-Wen;Holt, Carl;Holliday, L. Shannon;Gower, Laurie B.

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矿化胶原复合材料之所以引起人们的兴趣,是因为它们具有提供骨样支架的潜力,可以刺激自然的吸收和重塑过程。为了实现这一目标,我们的团队先前已经证明,骨的纳米结构可以使用聚合物诱导的液体前体(PILP)工艺来复制,这使得胶原蛋白与羟基磷灰石(HA)在纤维内矿化得以实现。先前的研究使用聚天冬氨酸(pASP),一种酸性非胶原蛋白(ncp)的简单模拟物,来产生纳米液滴/纳米颗粒,这种无晶态矿物前体可以渗透到i型胶原原纤维的间隙中。在这项研究中,我们表明骨桥蛋白(OPN)同样可以作为一种过程指导剂,用于胶原蛋白的纤维内矿化,尽管OPN通常被认为是矿化抑制剂。我们还发现,通过肌动蛋白环形成测量,在矿化过程中包含OPN可促进小鼠骨髓源性破骨细胞与先前脱矿的pilp再矿化骨的相互作用。当使用pASP作为过程导向剂时,破骨细胞激活发生,而使用OPN对破骨细胞激活产生显著影响,可能是因为OPN固有的精氨酸-甘氨酸-天冬氨酸(RGD)配体。通过利用OPN的多功能性,这些研究可能会导致生产具有可调整生物吸收率的仿生骨替代品的方法。
Mineralized collagen composites are of interest because they have the potential to provide a bone-like scaffold that stimulates the natural processes of resorption and remodeling. Working toward this goal, our group has previously shown that the nanostructure of bone can be reproduced using a polymer-induced liquid-precursor (PILP) process, which enables intrafibrillar mineralization of collagen with hydroxyapatite (HA) to be achieved. This prior work used polyaspartic acid (pASP), a simple mimic for acidic non-collagenous proteins (NCPs), to generate nanodroplets/nanoparticles of an amorphous mineral precursor which can infiltrate the interstices of type-I collagen fibrils. In this study we show that osteopontin (OPN) can similarly serve as a process-directing agent for the intrafibrillar mineralization of collagen, even though OPN is generally considered a mineralization inhibitor. We also found that inclusion of OPN in the mineralization process promotes the interaction of mouse marrow-derived osteoclasts with PILP-remineralized bone that was previously demineralized, as measured by actin ring formation. While osteoclast activation occurred when pASP was used as the process-directing agent, using OPN resulted in a dramatic effect on osteoclast activation, presumably because of the inherent arginine-glycine-aspartate acid (RGD) ligands of OPN. By capitalizing on the multifunctionality of OPN, these studies may lead the way to producing biomimetic bone substitutes with the capability of tailorable bioresorption rates.
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