Titanium nanotubes induce osteogenic differentiation through the FAK/RhoA/YAP cascade

Abstract

Clarifying mechanisms underlying various nanotopography-mediated changes in adherent cell function is requisite to understanding and improving the tissue–alloplastic interface for clinical applications. In this study, pure titanium foils and implants were modified with titanium nanotubes (TNTs) to verify their osteogenic abilities both in vitro and in vivo. The intracellular molecular dynamics of the FAK/RhoA/YAP cascade were assessed as a function of TNTs nanotopography. MC3T3-E1 cells adherent to large diameter TNTs presented limited cell spreading, reduced focal adhesions (FAs), and increased osteogenic differentiation, compared with those adherent to smooth Ti surfaces. Significant attenuation of FAK recruitment and RhoA activity was observed in TNTs adherent cells, and YAP localization moved from the nucleus to the cytoplasm. Moreover, YAP overexpression in MC3T3-E1 cells prevented TNTs-induced osteogenic differentiation. The demonstrated relationship between TNTs-mediated spreading behaviors, altered signaling through FAK and RhoA and YAP translocation suggests that nanotopographic cues influence osteoblastic differentiation in a YAP-dependent manner.