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可生物降解镁合金对人骨髓间充质干细胞成骨分化的影响。

The influence of biodegradable magnesium alloys on the osteogenic differentiation of human mesenchymal stem cells.

作者信息

Li Rachel W, Kirkland Nicholas T, Truong John, Wang Jian, Smith Paul N, Birbilis Nick, Nisbet David R

机构信息

The Medical School, The Australian National University, Acton, ACT 0200, Australia; John Curtin School of Medical Research, The Australian National University, Acton, ACT 0200, Australia.

出版信息

J Biomed Mater Res A. 2014 Dec;102(12):4346-57. doi: 10.1002/jbm.a.35111. Epub 2014 Feb 24.

DOI:10.1002/jbm.a.35111
PMID:24677428
Abstract

The postdegradation effect of pure Mg, Mg-1Y, Mg-5Al, and Mg-2Ca alloys on the differentiation, proliferation and gene expression of human mesenchymal stem cells (hMSCs) was investigated. It was revealed that that Mg(2+) ions result in an increase in cell proliferation. However, we observed a maximum concentration (approximately 8.0 × 10(-4) M) that was favourable to ATP production, above which ATP production began to decrease. In contrast to proliferation, no maximum concentration for osteogenic differentiation was observed, with increasing concentration of Mg(2+) ions resulting in an increase in osteogenic differentiation across the entire tested range. Interestingly, the Mg-2Ca alloy had minimal effect on osteogenic differentiation, with Mg-1Y and pure Mg having a superior effect on the proliferation and differentiation of hMSCs. This was also observed from gene expression data, where these alloys upregulated TGFβ-1, SMAD4, FGF-2, FGF-10, and BMP-2, while SOX-2, SOX-9, and TNF-α were downregulated. Increased expression of TGFβ-1, SMAD4, BMPs, and COLIA1 protein provided further evidence to support osteogenic differentiation and that the influence of the alloying extracts on differentiation may be via the SMAD signaling pathway.

摘要

研究了纯镁、Mg-1Y、Mg-5Al和Mg-2Ca合金降解后对人间充质干细胞(hMSCs)分化、增殖和基因表达的影响。结果表明,Mg(2+)离子可导致细胞增殖增加。然而,我们观察到有利于ATP产生的最大浓度(约8.0×10(-4) M),超过该浓度后ATP产生开始下降。与增殖情况相反,未观察到成骨分化的最大浓度,随着Mg(2+)离子浓度的增加,在整个测试范围内成骨分化均增加。有趣的是,Mg-2Ca合金对成骨分化的影响最小,Mg-1Y和纯镁对hMSCs的增殖和分化具有更好的作用。从基因表达数据中也观察到了这一点,这些合金上调了TGFβ-1、SMAD4、FGF-2、FGF-10和BMP-2,而下调了SOX-2、SOX-9和TNF-α。TGFβ-1、SMAD4、骨形态发生蛋白(BMPs)和COLIA1蛋白表达的增加为支持成骨分化提供了进一步的证据,并且合金提取物对分化的影响可能是通过SMAD信号通路实现的。

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