Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway
Osteogenic differentiation of bone marrow MSCs by β-tricalcium phosphate stimulating macrophages via BMP2 signalling pathway
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β-磷酸三钙通过 BMP2 信号通路刺激巨噬细胞诱导骨髓 MSC 成骨分化
DOI：
10.1016/j.biomaterials.2013.11.014
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发表时间：
2014-02-01
期刊：
影响因子：
14
通讯作者：
Xiao, Yin
中科院分区：
文献类型：
--
作者：
Chen, Zetao;Wu, Chengtie;Xiao, Yin
免疫反应在决定骨替代材料的体内命运中起重要作用，无论是在新骨形成还是炎性纤维组织包封中。骨替代材料的开发范式已从惰性材料转向免疫调节材料，强调免疫细胞在材料评价中的重要性。巨噬细胞是对植入物的免疫反应中的主要效应细胞，是骨生成不可或缺的，它们的异质性和可塑性使巨噬细胞成为免疫系统调节的主要靶点。然而，关于巨噬细胞在生物材料调控的成骨中的作用的报道很少。在这项研究中，我们使用β-磷酸三钙（β-TCP）作为模型生物材料，以研究巨噬细胞对材料刺激成骨的作用。巨噬细胞表型在对β-TCP提取物的响应中转变为M2极端，这与钙敏感受体（CaSR）通路的激活有关。骨形态发生蛋白2（BMP 2）也被β-TCP刺激显著上调，表明巨噬细胞可能参与β-TCP刺激的成骨。有趣的是，当巨噬细胞条件的β-TCP提取物应用于骨髓间充质干细胞（BMSCs）时，BMSCs的成骨分化显著增强，表明巨噬细胞在生物材料诱导的成骨中的重要作用。这些发现为材料刺激成骨的机制提供了有价值的见解，并为优化骨替代材料体外成骨能力的评价体系提供了策略。(C)2013爱思唯尔有限公司保留所有权利。
Immune reactions play important roles in determining the in vivo fate of bone substitute materials, either in new bone formation or inflammatory fibrous tissue encapsulation. The paradigm for the development of bone substitute materials has been shifted from inert to immunomodulatory materials, emphasizing the importance of immune cells in the material evaluation. Macrophages, the major effector cells in the immune reaction to implants, are indispensable for osteogenesis and their heterogeneity and plasticity render macrophages a primer target for immune system modulation. However, there are very few reports about the effects of macrophages on biomaterial-regulated osteogenesis. In this study, we used beta-tricalcium phosphate (beta-TCP) as a model biomaterial to investigate the role of macrophages on the material stimulated osteogenesis. The macrophage phenotype switched to M2 extreme in response to beta-TCP extracts, which was related to the activation of calcium-sensing receptor (CaSR) pathway. Bone morphogenetic protein 2 (BMP2) was also significantly upregulated by the beta-TCP stimulation, indicating that macrophage may participate in the beta-TCP stimulated osteogenesis. Interestingly, when macrophage-conditioned beta-TCP extracts were applied to bone marrow mesenchymal stem cells (BMSCs), the osteogenic differentiation of BMSCs was significantly enhanced, indicating the important role of macrophages in biomaterial-induced osteogenesis. These findings provided valuable insights into the mechanism of material-stimulated osteogenesis, and a strategy to optimize the evaluation system for the in vitro osteogenesis capacity of bone substitute materials. (C) 2013 Elsevier Ltd. All rights reserved.