Department of Stomatology, Navy Specialty Medical Center of Peoples' Liberation Army Navy, Shanghai 200052, People's Republic of China.
These authors contributed equally to this work.
Biomed Mater. 2020 Dec 18;16(1):015024. doi: 10.1088/1748-605X/abbfee.
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 TiO 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.
微纳形貌（MNT）可以促进干细胞的成骨分化，但形貌信号转导的机制尚不清楚。我们已经证实，MNT 作为一种应激源，会在大鼠骨髓间充质干细胞中引发内质网（ER）应激，并激活未折叠蛋白反应，而这种形貌诱导的 ER 应激会促进成骨分化。为了揭示纳米管尺寸对 ER 应激的影响，我们在纯钛（Ti）箔上制备了含有垂直取向的 TiO 纳米管的 MNT，其直径范围从 30nm 到 100nm，系统地研究了细胞的 ER 应激和成骨分化。培养 12 小时后，透射电子显微镜显示，MNT 上的细胞呈现出粗面内质网形态的明显扭曲，包含电子致密物质，并且随着纳米管尺寸的增加，内质网腔的扩张变得更加明显。此外，PCR 和 Western blot 显示，与 ER 应激相关的基因，即 ER 伴侣 78kDa 葡萄糖调节蛋白，也称为结合免疫球蛋白蛋白（GRP78/BiP），上调，这与 MNT 的成骨诱导能力一致。基于我们之前的研究，本文的发现进一步揭示了形貌线索调节细胞成骨分化的机制，这可能为优化植入物表面形貌的设计提供一种创新方法。
