School of Materials Science & Engineering, Southwest Jiaotong University, Chengdu 610031, China.
College of Medicine, Southwest Jiaotong University, Chengdu 610031, China.
Colloids Surf B Biointerfaces. 2022 Oct;218:112700. doi: 10.1016/j.colsurfb.2022.112700. Epub 2022 Jul 16.
Micro/nano-topography (MNT) is an important factor affecting cell response. Earlier studies using titania (TiO) nanotube as a model of MNT found that they mediated the differentiation of BMSCs into osteoblasts, but the mechanisms are not fully understood. Surprisingly, Periostin (Postn), a secreted protein involved in extracellular matrix (ECM) construction and promoting osteogenic differentiation of bone marrow stem cells (BMSCs), was previously observed to significantly up-regulated on TiO nanotube. We proposed that Postn may act as a MNT signal transduction role. In this study, we investigated the effect of MNT on Postn, and the influence of Postn on osteogenic differentiation-related genes through focal adhesion and downstream signals. It was found that, titanium (Ti) plates carrying TiO nanotubes with diameters of ∼100 nm (TNT-100) significantly up-regulated the expression of Postn compared with flat Ti. Furthermore, Postn activated the downstream focal adhesion kinase (FAK) signal pathway and β-catenin into the nucleus by interacting with integrin αV. Surprisingly, TNT-100 up-regulated the transcription level of Wnt3a, which was independent of the up-regulation of Postn. This new Postn signaling pathway may provide more insights into the signal transduction mechanism of MNT and development of biomaterials with improved osteogenic properties.
微纳形貌（MNT）是影响细胞反应的重要因素。早期使用二氧化钛（TiO）纳米管作为 MNT 模型的研究发现，它们介导骨髓间充质干细胞（BMSCs）向成骨细胞分化，但机制尚不完全清楚。令人惊讶的是，先前观察到细胞外基质（ECM）构建和促进骨髓干细胞（BMSCs）成骨分化的分泌蛋白骨粘连蛋白（Postn）在 TiO 纳米管上显著上调。我们提出 Postn 可能作为 MNT 信号转导的作用。在这项研究中，我们研究了 MNT 对 Postn 的影响，以及 Postn 通过粘着斑和下游信号对成骨分化相关基因的影响。结果发现，与平面 Ti 相比，直径约为 100nm 的 TiO 纳米管载钛板（TNT-100）显著上调了 Postn 的表达。此外，Postn 通过与整合素 αV 相互作用激活下游粘着斑激酶（FAK）信号通路和β-连环蛋白进入细胞核。令人惊讶的是，TNT-100 上调了 Wnt3a 的转录水平，而这与 Postn 的上调无关。这种新的 Postn 信号通路可能为 MNT 的信号转导机制和具有改善成骨性能的生物材料的发展提供更多的见解。
