TiO2 nanotube topography enhances osteogenesis through filamentous actin and XB130-protein-mediated mechanotransduction

Abstract

TiO₂ nanotube topography, as nanomechanical stimulation, can significantly promote osteogenesis and improve the osteointegration on the interface of implants and bone tissue. However, the underlying mechanism has not been fully elucidated. XB130 is a member of the actin filament-associated protein family and is involved in the regulation of cytoskeleton and tyrosine kinase-mediated signalling as an adaptor protein. Whether XB130 is involved in TiO₂ nanotubes-induced osteogenic differentiation and how it functions in mechano-biochemical signalling transduction remain to be elucidated. In this study, the role of XB130 on TiO₂ nanotube-induced osteogenesis and mechanotransduction was systematically investigated. TiO₂ nanotube topography was fabricated via anodic oxidation and characterized. The osteogenic effect was significantly accelerated by the TiO₂ nanotube surface in vitro and vivo. XB130 was significantly upregulated during this process. Moreover, XB130 overexpression significantly promoted osteogenic differentiation, whereas its knockdown inhibited it. Filamentous actin depolymerization could change the expression and distribution of XB130, thus affecting osteogenic differentiation. Mechanistically, XB130 could interact with Src and result in the activation of the downstream PI3K/Akt/GSK-3β/β-catenin pathway, which accounts for the regulation of osteogenesis. This study for the first time showed that the enhanced osteogenic effect of TiO₂ nanotubes could be partly due to the filamentous actin and XB130 mediated mechano-biochemical signalling transduction, which might provide a reference for guiding the design and modification of prostheses to promote bone regeneration and osseointegration. STATEMENT OF SIGNIFICANCE: TiO₂ nanotubes topography can regulate cytoskeletal rearrangement and thus promote osteogenic differentiation of BMSCs. However, how filamentous actin converts mechanical stimulus into biochemical activity remains unclear. XB130 is a member of actin filament-associated protein family and involves in the regulation of tyrosine kinase-mediated signalling. Therefore, we hypothesised that XB130 might bridge the mechano-biochemical signalling transduction during TiO₂ nanotubes-induced osteogenic differentiation. For the first time, this study shows that TiO₂ nanotubes enhance osteogenesis through filamentous actin and XB130 mediated mechanotransduction, which provides new theoretical basis for guiding the design and modification of prostheses to promote bone regeneration and osseointegration.

Keywords: F-actin; Osteogenic differentiation; PI3K/Akt/GSK-3β/β-catenin signalling pathway; TiO(2) nanotubes; XB130.