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纳米拓扑线索通过 BMP-2 中间产物介导病毒基底上干细胞的成骨作用。

Nanotopographical Cues Mediate Osteogenesis of Stem Cells on Virus Substrates through BMP-2 Intermediate.

机构信息

Department of Chemistry and Biochemistry , University of South Carolina , 631 Sumter Street , Columbia , South Carolina 29208 , United States.

Joint Department of Biomedical Engineering , University of North Carolina at Chapel Hill and North Carolina State University , Chapel Hill , North Carolina 27599 , United States.

出版信息

Nano Lett. 2019 Dec 11;19(12):8372-8380. doi: 10.1021/acs.nanolett.9b02001. Epub 2019 Jul 24.

DOI:10.1021/acs.nanolett.9b02001
PMID:31296009
Abstract

Recent studies have demonstrated rapid osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) on substrates with plant virus modified nanotopographical cues as a promising strategy for bone repair; however, the mechanisms remain unclear. We hypothesized that the highly structurally ordered virus coat proteins, responsible for targeting specific cellular components, are critical for the osteogenesis promotion. In this study, hybrid viral gold nanorods were prepared to explore the effects of highly ordered arranged virus coat proteins on osteogenic differentiation of BMSCs. The results herein indicate that it is the nanotopographical cues modified by structurally ordered virus nanoparticles, not the chemical properties of virus surface, that mediate osteogenesis. Bone morphogenetic protein 2 (BMP-2) expression is significantly increased and serves as a modulator that mediates the osteogenic differentiation in response to the viral particle coatings. After BMP-2 is inhibited by Noggin, the osteogenesis promoting effects are significantly compromised, demonstrated by lower alkaline phosphatase activity and calcium sequestration. This study reveals that plant virus modified nanotopographical substrates promote osteogenic differentiation of BMSCs through increasing BMP-2 autocrine. It provides key insights to engineering functional materials for rapid bone repair.

摘要

最近的研究表明,骨髓间充质干细胞(BMSCs)在具有植物病毒修饰的纳米形貌线索的基质上具有快速成骨分化的特性,这是一种有前途的骨修复策略;然而,其机制尚不清楚。我们假设,负责靶向特定细胞成分的高度有序的病毒外壳蛋白对于促进成骨作用至关重要。在这项研究中,制备了杂交病毒金纳米棒,以探讨高度有序排列的病毒外壳蛋白对 BMSCs 成骨分化的影响。本文的研究结果表明,介导成骨作用的是结构有序的病毒纳米颗粒修饰的纳米形貌线索,而不是病毒表面的化学性质。骨形态发生蛋白 2(BMP-2)的表达显著增加,并作为一种调节剂,介导对病毒颗粒涂层的成骨分化。在 Noggin 抑制 BMP-2 后,碱性磷酸酶活性和钙摄取降低,表明成骨促进作用显著受损。这项研究表明,植物病毒修饰的纳米形貌底物通过增加 BMP-2 自分泌促进 BMSCs 的成骨分化。它为快速骨修复的功能材料工程提供了重要的见解。

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