Surface Topography Regulates Osteogenic Differentiation of MSCs via Crosstalk between FAK/MAPK and ILK/beta-Catenin Pathways in a Hierarchically Porous Environment
Surface Topography Regulates Osteogenic Differentiation of MSCs via Crosstalk between FAK/MAPK and ILK/beta-Catenin Pathways in a Hierarchically Porous Environment
复制标题
表面形貌通过分层多孔环境中 FAK/MAPK 和 ILK/β-Catenin 通路之间的串扰调节 MSC 的成骨分化
DOI：
10.1021/acsbiomaterials.7b00315
复制
发表时间：
2017
影响因子：
--
通讯作者：
Liu Changsheng
中科院分区：
文献类型：
--
作者：
Niu Haoyi;Lin Dan;Tang Wei;Ma Yifan;Duan Bing;Yuan Yuan;Liu Changsheng
间充质干细胞（MSCs）对三维环境中复杂微结构的反应及其分子机制尚不清楚。在这里，与分级介孔生物活性玻璃（MBG）支架作为基板模型，我们显示了特定的，精心制作的微观形貌（微颗粒，微孔和混合微颗粒/微孔表面）对MSC成骨的影响和所涉及的分子机制。在尺寸和密度相近的情况下，微孔表面更有利于MSC的成骨，微颗粒/微孔混合表面表现出协同效应。所有的微尺度形貌都促进了整合素亚基、粘着斑复合物的表达，并上调了FAK/MAPK和ILK/β-catenin信号通路。分别阻断FAK/MAPK和ILK/β-catenin级联反应可显著减弱增强的β-catenin信号传导，并分别减弱ERK 1/2和P38的磷酸化，表明FAK/MAPK和ILK/β-catenin信号传导之间存在典型的串扰。将MSC的反应与特定的地形学线索相关联，可以推断，微颗粒/微孔地形学诱导了FA的组装和稳态，因此FAK/MAPK和ILK/β-catenin信号传导在调节MSC成骨分化中起关键作用。因此，这些发现对于更好地理解MSC在3D环境中的命运具有重要意义，并为开发用于骨再生的新型生物材料提供指导。
The response of mesenchymal stem cell (MSCs) to elaborate microarchitectured topographies in three-dimensional environment and the underlying molecular mechanism remain poorly understood. Here, with hierarchical mesoporous bioactive glass (MBG) scaffolds as substrate model, we show the effects of specific, elaborate microtextured topographies (micrograiny, microporous and hybrid micrograiny/microporous surface) on MSCs osteogenesis and the molecular mechanism involved. With a similar size and density, the microporous surface was more favorable for the MSC osteogenesis, and the hybrid micrograiny/microporous surface exhibited a synergetic effect. All the microscaled topographies facilitated expression of integrin subunits, focal adhesion complexes, and up-regulated FAK/MAPK and ILK/β-catenin signaling pathways. Separately blocking FAK/MAPK and ILK/β-catenin cascade dramatically attenuated the heightened β-catenin signaling, and the phosphorylation of ERK1/2 and P38, respectively, indicating a typical crosstalk between FAK/MAPK and ILK/β-catenin signalings was involved. Correlating the MSCs response with the specific topographical cues, it can be inferred that the micrograiny/microporous topographies induced FAs assembly and homeostasis, and thus FAK/MAPK and ILK/β-catenin signalings played critical role in regulating MSCs osteogenic differentiation. The findings, therefore, have significant implications in better understanding of the MSCs fate in a 3D environment and provided guidance of the development of novel biomaterial for bone regeneration.