Stem Cells：锶可促进间充质干细胞成骨分化

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2011年6月的国际学术期刊《干细胞》（Stem Cells）发表了中国科学院深圳先进技术研究院医工所王立平和蔡林涛研究组的研究论文，他们在锶促进间充质干细胞成骨分化及掺锶材料修复骨缺损的效果和机制研究中取得新成果。本项研究的部分成果已同时被国外Mason RS研究组证实（Journal of Biological Chemistry, 2011年5月12日）。
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) _. D) \, U2 c4 J' x( [/ ^该工作由杨帆、杨大志、屠洁等共同完成。此研究工作的掺锶原材料由香港大学医学院骨科系吕维加教授（W. William .Lu）提供。% V3 X$ [. d2 [

' U0 I: f+ C5 N2 O锶及其化合物具有的重要成骨作用近年已经得到重视，锶在促进成骨细胞活性的同时可以抑制破骨细胞的活性，对骨生成的诱导能力强，引起新生骨量增多。另外，掺锶生物材料具有良好的生物相容性和较强的诱导骨生成的能力。间充质细胞作为成体干细胞的重要组成部分，具有良好的成骨分化潜能和广阔的市场应用价值。目前关注的问题是：锶是否可以有效促进间充质细胞体外和体内进行成骨分化，其具体的分子机制是什么？这些问题都有待于深入研究。
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7 i' y+ S4 f# m+ D" `3 l杨帆等首先发现，锶具有可以促进间充质细胞体外成骨分化能力。在锶作用下，细胞碱性磷酸酶染色增强，细胞外胶原成分表达升高，Wnt通路中的信号分子β－catenin和受体Frizzled 8基因转录水平升高。在体动物研究中，研究人员构建了胶原和掺锶羟基磷灰石复合支架，提高了材料的可塑性，胶原体内降解的同时可以形成有效孔径，促使间充质干细胞和锶的有效接触。把掺锶复合材料植入大鼠颅骨缺损模型后，同单纯的胶原羟基磷灰石材料相比，影像学显示锶材料促使新生骨密度增加，组织学发现新生骨的质量和数量都有较为明显的提高。免疫组织化学显示，新生骨修复部位的胶原成分明显增多，β－catenin分子的表达增强。体外和体内的研究表明，锶可以通过影响Wnt通路来促进间充质细胞的成骨进程。& x. r+ L, d( U: v6 C( a& j
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本研究进一步揭示了锶促进间充质细胞成骨分化的分子机制。所构建的复合生物材料结合了锶的诱导成骨能力和胶原的自身的可降解性，有较好的成骨促进作用，为临床修复骨缺损的生物材料支架研究提供了新的可能性。完成此项目的实验室分别是深圳市神经精神调控重点实验室和癌症纳米重点实验室。（生物谷Bioon.com）
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3 V' X0 k- Q) @5 c$ i8 b* _9 N生物谷推荐原文 出处：
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# P  [, V1 B( b8 NSTEM CELLS    DOI： 10.1002/stem.646
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Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling1 K/ T+ s& E% a) \7 I0 m$ U* S- ?
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Yang, Fan; Yang, Dazhi; Tu, Jie; Zheng, Qixin; Cai, Lintao; Wang, Liping
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: ~0 p8 h7 D: }& HKeywords:Strontium;Mesenchymal stem cells;Wnt/β‐CateninAbstractStrontium ranelate is a newly approved drug that can reduce the risk of vertebral fracture, which is attributed to its dual function in increasing the bone formation and decreasing the bone resorption. Strontium‐containing hydroxyapatite was also demonstrated to stimulate the osteoblast activity and inhibit the osteoclast activity. However, the molecular mechanisms of strontium underlying such beneficial effects were still not fully understood. In this study, we investigated the effects of strontium on the osteogenic differentiation of human mesenchymal stem cells (MSCs) and its related mechanism; its osteogenic potential was also evaluated using a calvarial defect model in rats. We found that strontium could enhance the osteogenic differentiation of the MSCs, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/β‐catenin pathway. After transplanting the collagen‐strontium‐substituted hydroxyapatite scaffold into the bone defect region, histology and computed tomography scanning revealed that in vivo bone formation was significantly enhanced; the quantity of mature and remodeled bone substantially increased and ECM accumulated. Interestingly, strontium induced an increase of β‐catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the β‐catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation. STEM CELLS 2011;29:981–9915 _4 S; w1 o3 f! t" S, {
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