材料刚度能够诱导干细胞的成骨分化，但对于在诱导过程中刚度物理信号如何引导细胞定向分化的机制所知甚少。我们发现在材料刚度诱导干细胞成骨分化过程中，整合素α5、β1起到重要作用，因此其下游关键分子的解析已成为下一步研究的重要内容。诱导性多能干细胞（iPSCs）已成为生物材料和组织工程研究的种子细胞。ECM刚度指导iPSCs成骨分化的调控成为生物材料学新的研究方向。本项目拟用已获得的人毛囊iPSCs和人骨髓MSC，在稳定的ECM刚度梯度体系上，采用分子生物学结合生物信息学策略，系统研究ECM刚度对iPSCs和MSC成骨分化的影响；分析ECM刚度通过整合素诱导iPSCs和MSCs成骨分化中基因表达谱的分子网络框架，以实现物理信号与iPSCs分化的生物信号的“对接”；并采用过/低表达目标基因方法进行验证。此研究为揭示机械刚度诱导干细胞成骨分化的机制及新型ECM仿生材料的合成提供科学基础。

The material elasticity can induce the osteogenic differentiation of stem cells, but we still know little about the mechanism how the physical signals guide stem cells differentiation. We prove integrin α5 β1 may play an important role in this program. The key downstream molecules and network analysis become an important part of future research. Induced pluripotent stem cells (iPSCs) have become useful in biomaterials and tissue engineering research. Osteogenic differentiation of iPSCs guided by extracellular matrix (ECM) elasticity becomes an ideal model in the field. The project intends to culture human human hair follicle-derived iPSCs and human bone marrow MSC on the gradient elasticity, define the appropriate elasticity for osteogenic differentiation, and combine the molecular biology and bioinformatics strategies. We shall focus on the systematic impact of ECM elasticity on osteogenic differentiation of iPSCs and MSCs. The molecular networks framework induced by ECM elasticity through integrin is based on the gene expression profiles of osteogenic differentiation of iPSCs and MSCs in order to achieve the "docking" of physical signals and biological signals; and will be verified by up / down-regulated expression of target genes , activation / inhibition of target gene activity and other methods. Our studies will provide the scientific basis for revealing the mechanism of the elasticity-induced osteogenic differentiation of stem cells and synthesing the new biomaterials.