TiO₂ nanotube enhance osteogenesis through Kindlin-2/Integrin β1/YAP pathway-mediated mechanotransduction

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.