2011年6月的國(guó)際學(xué)術(shù)期刊《干細(xì)胞》（Stem Cells）發(fā)表了中國(guó)科學(xué)院深圳先進(jìn)技術(shù)研究院醫(yī)工所王立平和蔡林濤研究組的研究論文,，他們?cè)阪J促進(jìn)間充質(zhì)干細(xì)胞成骨分化及摻鍶材料修復(fù)骨缺損的效果和機(jī)制研究中取得新成果,。本項(xiàng)研究的部分成果已同時(shí)被國(guó)外Mason RS研究組證實(shí)（Journal of Biological Chemistry, 2011年5月12日）,。
該工作由楊帆、楊大志,、屠潔等共同完成,。此研究工作的摻鍶原材料由香港大學(xué)醫(yī)學(xué)院骨科系呂維加教授（W. William .Lu）提供,。
鍶及其化合物具有的重要成骨作用近年已經(jīng)得到重視,，鍶在促進(jìn)成骨細(xì)胞活性的同時(shí)可以抑制破骨細(xì)胞的活性,，對(duì)骨生成的誘導(dǎo)能力強(qiáng)，引起新生骨量增多,。另外,，摻鍶生物材料具有良好的生物相容性和較強(qiáng)的誘導(dǎo)骨生成的能力。間充質(zhì)細(xì)胞作為成體干細(xì)胞的重要組成部分,，具有良好的成骨分化潛能和廣闊的市場(chǎng)應(yīng)用價(jià)值。目前關(guān)注的問(wèn)題是：鍶是否可以有效促進(jìn)間充質(zhì)細(xì)胞體外和體內(nèi)進(jìn)行成骨分化,，其具體的分子機(jī)制是什么,？這些問(wèn)題都有待于深入研究。
楊帆等首先發(fā)現(xiàn),，鍶具有可以促進(jìn)間充質(zhì)細(xì)胞體外成骨分化能力,。在鍶作用下，細(xì)胞堿性磷酸酶染色增強(qiáng),，細(xì)胞外膠原成分表達(dá)升高,，Wnt通路中的信號(hào)分子β－catenin和受體Frizzled 8基因轉(zhuǎn)錄水平升高。在體動(dòng)物研究中，研究人員構(gòu)建了膠原和摻鍶羥基磷灰石復(fù)合支架,，提高了材料的可塑性,，膠原體內(nèi)降解的同時(shí)可以形成有效孔徑，促使間充質(zhì)干細(xì)胞和鍶的有效接觸,。把摻鍶復(fù)合材料植入大鼠顱骨缺損模型后,，同單純的膠原羥基磷灰石材料相比，影像學(xué)顯示鍶材料促使新生骨密度增加,，組織學(xué)發(fā)現(xiàn)新生骨的質(zhì)量和數(shù)量都有較為明顯的提高,。免疫組織化學(xué)顯示，新生骨修復(fù)部位的膠原成分明顯增多,，β－catenin分子的表達(dá)增強(qiáng),。體外和體內(nèi)的研究表明，鍶可以通過(guò)影響Wnt通路來(lái)促進(jìn)間充質(zhì)細(xì)胞的成骨進(jìn)程,。
本研究進(jìn)一步揭示了鍶促進(jìn)間充質(zhì)細(xì)胞成骨分化的分子機(jī)制,。所構(gòu)建的復(fù)合生物材料結(jié)合了鍶的誘導(dǎo)成骨能力和膠原的自身的可降解性，有較好的成骨促進(jìn)作用,，為臨床修復(fù)骨缺損的生物材料支架研究提供了新的可能性,。完成此項(xiàng)目的實(shí)驗(yàn)室分別是深圳市神經(jīng)精神調(diào)控重點(diǎn)實(shí)驗(yàn)室和癌癥納米重點(diǎn)實(shí)驗(yàn)室。（生物谷Bioon.com）
生物谷推薦原文 出處：
STEM CELLS DOI： 10.1002/stem.646
Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling
Yang, Fan; Yang, Dazhi; Tu, Jie; Zheng, Qixin; Cai, Lintao; Wang, Liping
Keywords: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;29:981–991
