Deng Qing, Yao Quanzhou, Wu Anhang, Li Jinsheng, Li Yingying, Tang Lingling, Zeng Huanghe, Chen Song, Guo Tailin
College of Medicine , Southwest Jiaotong University, No. 111, North Section 1, Second Ring Road, Chengdu, Sichuan, 610031, CHINA.
Medical Engineering Department, People's Liberation Army The General Hospital of Western Theater Command, 270 Tianhuan Road, Rongdu Avenue, Chengdu, Sichuan, 610083, CHINA.
Biomed Mater. 2024 Sep 23. doi: 10.1088/1748-605X/ad7e8f.
Titanium has been widely employed in the fields of orthopaedics and dentistry, attributed to its superior mechanical and biological properties. The mechanical stimulation induced by the titanium dioxide (TiO2) nanotubes (TNTs) morphology resulting from surface modification has been demonstrated to enhance the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Kindlin-2, a pivotal focal adhesion protein, is involved in mechanical signaling processes through the regulation of stress fibril filament assembly. Additional research is needed to clarify the involvement of Kindlin-2 in the mechanism of TNTs-induced osteogenic differentiation. This study systematically investigated the impact of Kindlin-2 on TNTs-induced osteogenesis and mechanotransduction. TiO2 nanotubes with diameters of approximately 30 nm (TNT-30) and 100 nm (TNT-100) were fabricated and characterized using anodic oxidation. The results showed that TNT-100 significantly increased the expression of Kindlin-2 and enhanced osteogenic differentiation compared to polished titanium (PT) and TNT-30. Additionally, Kindlin-2 promotes cytoskeleton assembly by regulating the integrin β1/FAK/RhoA signaling pathway, impacting osteogenic gene expression and BMSC differentiation in a Yes-Associated Protein (YAP)-dependent manner. Therefore, these findings contribute to a more comprehensive understanding of the fate of BMSCs on TNTs morphologies and provide a novel theoretical foundation for the development of advanced bone repair biomaterials.
由于其优异的机械性能和生物学特性，钛已在骨科和牙科领域得到广泛应用。表面改性产生的二氧化钛（TiO₂）纳米管（TNTs）形态所诱导的机械刺激已被证明可增强骨髓间充质干细胞（BMSCs）的成骨分化。Kindlin-2是一种关键的粘着斑蛋白，通过调节应力纤维丝组装参与机械信号传导过程。需要进一步研究以阐明Kindlin-2在TNTs诱导的成骨分化机制中的作用。本研究系统地研究了Kindlin-2对TNTs诱导的成骨作用和机械转导的影响。使用阳极氧化法制备并表征了直径约为30 nm（TNT-30）和100 nm（TNT-100）的TiO₂纳米管。结果表明，与抛光钛（PT）和TNT-30相比，TNT-100显著增加了Kindlin-2的表达并增强了成骨分化。此外，Kindlin-2通过调节整合素β1/FAK/RhoA信号通路促进细胞骨架组装，以Yes相关蛋白（YAP）依赖的方式影响成骨基因表达和BMSC分化。因此，这些发现有助于更全面地了解BMSCs在TNTs形态上的命运，并为先进骨修复生物材料的开发提供新的理论基础。
