College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.
Key Laboratory of Advanced Technologies of Materials (MOE), School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
Colloids Surf B Biointerfaces. 2019 Oct 1;182:110332. doi: 10.1016/j.colsurfb.2019.06.061. Epub 2019 Jun 28.
Micro/nano-topography (MNT) is an important variable affecting osseointegration of bone biomaterials, but the underlying mechanisms are not fully understood. We probed the role of a AMOT130/YAP pathway in osteoblastic differentiation of bone marrow mesenchymal stems cultured on titanium (Ti) carrying MNTs. Ti surfaces with two well-defined MNTs (TiO2 nanotubes of different diameters and wall thicknesses) were prepared by anodization. Rat BMSCs were cultured on flat Ti and Ti surfaces carrying MNTs, and cell behaviors (i.e., morphology, F-actin development, osteoblastic differentiation, YAP localization) were studied. Ti surfaces carrying MNTs increased F-actin formation, osteoblastic gene expression, and protein AMOT130 production in BMSCs (all vs. flat Ti), and the surface carrying larger nantubes was more effective, confirming osteoblastic differentiation induced by MNTs. Elevation of the AMOT130 level (by inhibiting its degradation) increased the osteoblastic gene expression, F-actin formation, and nuclear localization of YAP. These show that, AMOT130/YAP is an important pathway mediating the translation of MNT signals to BMSC osteoblastic commitment, likely via the cascade: AMOT130 promotion of F-actin formation, increased YAP nuclear import, and activation of osteoblastic gene expression.
微/纳形貌（MNT）是影响骨生物材料骨整合的一个重要变量，但其中的机制尚不完全清楚。我们探讨了 AMOT130/YAP 通路在骨髓间充质干细胞（BMSCs）向带有 MNTs 的钛（Ti）上的成骨分化中的作用。通过阳极氧化法制备了具有两种明确 MNTs（不同直径和壁厚的 TiO2 纳米管）的 Ti 表面。将大鼠 BMSCs 培养在平面 Ti 和带有 MNTs 的 Ti 表面上，研究细胞行为（形态、F-actin 发育、成骨分化、YAP 定位）。携带 MNTs 的 Ti 表面增加了 BMSCs 中的 F-actin 形成、成骨基因表达和蛋白 AMOT130 的产生（均与平面 Ti 相比），且带有较大纳米管的表面更有效，证实了 MNTs 诱导的成骨分化。升高 AMOT130 水平（通过抑制其降解）增加了成骨基因表达、F-actin 形成和 YAP 的核定位。这些表明，AMOT130/YAP 是将 MNT 信号转化为 BMSC 成骨分化的重要途径，可能通过级联反应实现：AMOT130 促进 F-actin 形成，增加 YAP 核内输入，并激活成骨基因表达。
