Osteogenic Response to BMP-2 of hMSCs Grown on Apatite-Coated Scaffolds
Osteogenic Response to BMP-2 of hMSCs Grown on Apatite-Coated Scaffolds
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DOI：
10.1002/bit.23227
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发表时间：
2011-11-01
影响因子：
3.8
通讯作者：
Leach, J. Kent
中科院分区：
文献类型：
--
作者：
Davis, Hillary E.;Case, Erin M.;Leach, J. Kent
骨传导材料在促进与周围骨组织的整合以及由此产生的体内骨修复中起关键作用。然而，与可溶性信号结合的3D骨传导基质对祖细胞分化的影响尚不清楚。在这项研究中，我们研究了骨形态发生蛋白-2（BMP-2）浓度对人骨髓间充质干细胞（hMSCs）成骨分化的影响，当接种在碳酸化磷灰石涂层聚合物支架上时。与非矿化支架相比，矿化支架更具亲水性，并吸附更多的BMP-2。碱性磷酸酶（ALP）活性的变化在刺激的hMSCs依赖于剂量的BMP-2和支架组合物。我们在所有时间点检测到矿化支架上更多的细胞分泌钙，更高的BMP-2浓度导致ALP和钙水平增加。RUNX 2和IBSP基因在hMSCs中的表达受底物和可溶性信号的影响，SP 7受可溶性因子的影响，而BMP 1受底物介导的信号的影响。目前的数据表明，磷灰石和BMP-2的组合不简单地增强hMSCs的成骨反应，但通过多种途径，可能是底物和生长因子介导的。因此，多种信号传导策略可能是实现最佳骨再生所必需的。Biotechnol. Bioeng. 2011; 108：2727-2735。(C)2011 Wiley Periodicals，Inc.
Osteoconductive materials play a critical role in promoting integration with surrounding bone tissue and resultant bone repair in vivo. However, the impact of 3D osteoconductive substrates coupled with soluble signals on progenitor cell differentiation is not clear. In this study, we investigated the influence of bone morphogenetic protein-2 (BMP-2) concentration on the osteogenic differentiation of human mesenchymal stem cells (hMSCs) when seeded in carbonated apatite-coated polymer scaffolds. Mineralized scaffolds were more hydrophilic and adsorbed more BMP-2 compared to non-mineralized scaffolds. Changes in alkaline phosphatase (ALP) activity within stimulated hMSCs were dependent on the dose of BMP-2 and the scaffold composition. We detected more cell-secreted calcium on mineralized scaffolds at all time points, and higher BMP-2 concentrations resulted in increased ALP and calcium levels. RUNX2 and IBSP gene expression within hMSCs was affected by both substrate and soluble signals, SP7 by soluble factors, and SPARC by substrate-mediated cues. The present data indicate that a combination of apatite and BMP-2 do not simply enhance the osteogenic response of hMSCs, but act through multiple pathways that may be both substrate-and growth factor-mediated. Thus, multiple signaling strategies will likely be necessary to achieve optimal bone regeneration. Biotechnol. Bioeng. 2011; 108: 2727-2735. (C) 2011 Wiley Periodicals, Inc.