Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface.
Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface.
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镁取代羟基磷灰石表面促进骨形态发生蛋白-2的受体识别并增强其生物活性
DOI：
10.1038/srep24323
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发表时间：
2016-04-14
影响因子：
4.6
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Huang B;Yuan Y;Li T;Ding S;Zhang W;Gu Y;Liu C
骨形态发生蛋白-2(BMP-2)功能化的生物材料表面是构建成功的骨科植入物/支架的一种有前途的方法。然而，BMP-2在材料表面的生物活性还远远不能令人满意，相关的蛋白质-表面相互作用的机制仍然不清楚。基于应用最广泛的植骨/支架材料羟基磷灰石(HAP)，我们开发了一种镁取代羟基磷灰石基质(MG-HAP，2.2at%取代度)来解决这些问题。此外，我们还研究了重组人骨形态发生蛋白-2(rhBMP-2)在羟基磷灰石和镁-羟基磷灰石表面的吸附动力学、骨形态发生蛋白的募集和生物活性。通过分子动力学模拟计算了BMP-2吸附分子的择优取向、构象变化和半胱氨酸结的稳定性。结果表明，与羟基磷灰石相比，镁-羟基磷灰石表面的重组人骨形成蛋白-2具有更强的生物活性，更容易识别BMPRs和更高的碱性磷酸酶活性。此外，分子模拟表明BMP-2在羟基磷灰石和镁-羟基磷灰石表面具有不同的侧向取向。有趣的是，镁-羟基磷灰石表面的BMP-2很大程度上保留了活性蛋白质结构，证明其半胱氨酸结比在羟基磷灰石表面更稳定。这些发现清楚地阐明了BMP-2-HAP/mg-HAP相互作用的机制，突出了Mg-HAP/BMP-2基质在骨再生植入物/支架中的应用前景。
Biomaterial surface functionalized with bone morphogenetic protein-2 (BMP-2) is a promising approach to fabricating successful orthopedic implants/scaffolds. However, the bioactivity of BMP-2 on material surfaces is still far from satisfactory and the mechanism of related protein-surface interaction remains elusive. Based on the most widely used bone-implants/scaffolds material, hydroxyapatite (HAP), we developed a matrix of magnesium-substituted HAP (Mg-HAP, 2.2 at% substitution) to address these issues. Further, we investigated the adsorption dynamics, BMPRs-recruitment, and bioactivity of recombinant human BMP-2 (rhBMP-2) on the HAP and Mg-HAP surfaces. To elucidate the mechanism, molecular dynamic simulations were performed to calculate the preferred orientations, conformation changes, and cysteine-knot stabilities of adsorbed BMP-2 molecules. The results showed that rhBMP-2 on the Mg-HAP surface exhibited greater bioactivity, evidenced by more facilitated BMPRs-recognition and higher ALP activity than on the HAP surface. Moreover, molecular simulations indicated that BMP-2 favoured distinct side-on orientations on the HAP and Mg-HAP surfaces. Intriguingly, BMP-2 on the Mg-HAP surface largely preserved the active protein structure evidenced by more stable cysteine-knots than on the HAP surface. These findings explicitly clarify the mechanism of BMP-2-HAP/Mg-HAP interactions and highlight the promising application of Mg-HAP/BMP-2 matrixes in bone regeneration implants/scaffolds.