Micro/nano-topography (MNT) can promote osteogenic differentiation of stem cells, but the mechanism of topographical signaling transduction remains unclear. We have confirmed MNT, as a stressor, triggers endoplasmic reticulum (ER) stress and activates unfolded protein response in rat bone marrow mesenchymal stem cells, and such topography-induced ER stress promotes osteogenic differentiation. In order to reveal the influence of nanotube dimensions on ER stress, MNTs containing vertically oriented TiO₂ nanotubes of diameters ranging from 30 nm to 100 nm were fabricated on pure titanium (Ti) foils, and ER stress and osteogenic differentiation of cells were systematically studied. After 12 h of cultivation, the transmission electron microscopy showed that cells on MNTs presented gross distortions of rough ER morphology containing the electron-dense material, and the expansion of the ER lumen became more pronounced as the dimension of nanotubes increased. Additionally, PCR and western blotting showed that the ER stress-related gene, the ER chaperone 78 kDa glucose-regulated protein, also known as binding-immunoglobulin protein (GRP78/BiP), was up-regulated, which was consistent with the osteogenesis-inducing ability of MNTs. Based on our previous studies, the findings in this article further revealed the mechanism for topographical cues modulating osteogenic differentiation of cells, which may provide an innovative approach for the optimal design of implant surface topography.

微/纳米拓扑结构（MNT）可以促进干细胞的成骨分化，但拓扑结构信号转导的机制仍不清楚。我们已经证实MNT作为一种应激源，会引发大鼠骨髓间充质干细胞的内质网（ER）应激并激活未折叠蛋白反应，而这种地形诱导的ER应激可促进成骨分化。为了揭示纳米管尺寸对内质网应力的影响，在纯钛（Ti）箔上制备了含有垂直取向的直径为30 nm至100 nm的TiO ₂纳米管的MNT，系统地研究了内质网应力和细胞的成骨分化。 。培养12小时后，透射电子显微镜显示MNT上的细胞呈现出含有电子致密材料的粗糙内质网形态的严重扭曲，并且随着纳米管尺寸的增加，内质网管腔的扩张变得更加明显。此外，PCR和蛋白质印迹显示内质网应激相关基因，即内质网伴侣78 kDa葡萄糖调节蛋白，也称为结合免疫球蛋白（GRP78/BiP），表达上调，这与成骨作用一致。 MNT 的诱导能力。基于我们之前的研究，本文的研究结果进一步揭示了地形信号调节细胞成骨分化的机制，这可能为种植体表面形貌的优化设计提供创新方法。