Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling
Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling
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锶通过激活 Wnt/Catenin 信号传导增强间充质干细胞的成骨分化和体内骨形成
DOI：
10.1002/stem.646
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发表时间：
2011-06-01
期刊：
影响因子：
5.2
通讯作者：
Wang, Liping
中科院分区：
文献类型：
--
作者：
Yang, Fan;Yang, Dazhi;Wang, Liping
雷奈酸锶是一种新批准的降低椎体骨折风险的药物，这归因于其促进骨形成和减少骨吸收的双重作用。含锶羟基磷灰石也被证明可以刺激成骨细胞活性和抑制破骨细胞活性。然而，锶这种有益作用的分子机制仍然没有完全理解。在这项研究中，我们研究了锶对人骨髓间充质干细胞（MSCs）的成骨分化及其相关机制的影响，其成骨潜能也评估了使用大鼠颅骨缺损模型。我们发现锶可以促进MSC的成骨分化，上调细胞外基质（ECM）基因表达和激活Wnt/β-catenin通路。将胶原-锶-取代的羟基磷灰石支架植入骨缺损区域后，组织学和计算机断层扫描显示体内骨形成显著增强;成熟和重塑骨的数量大幅增加，ECM积累。有趣的是，锶诱导新形成的骨区域中β-连环蛋白表达的增加。在本研究中，我们首次发现锶可以在体外和体内刺激β-catenin的表达，这可能有助于增强MSCs的成骨分化和体内骨形成。干细胞2011;29：981-991
Strontium 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/beta-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 beta-catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the beta-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