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    Betal-integrin/Hedgehog-Glil signaling pathway fuels the diameter-dependent osteoblast differentiation on different TiO2 nanotubes The optimal-diameter nanotubes for osteoblast differentiation

    Year: 2021

    Journal: Int. J. Biochem. Cell Biol., Volume 137, AUG

    Authors: Xie, Yirui; Chen, Xiaozhu; Zheng, Xuying; Li, Ling; Li, Jieyin; Xu, Yuling; He, Junbing; Lin, Yao

    Organizations: Science and Technology Planning Project of Jieyang City [2019ws060]; Natural Science Foundation of Guangdong Province [2020A1515010109]; Guangdong Prov-ince Science and Technology Special Fund of Major Projects and Task List in Jieyang City [xgfy021]

    Keywords: Surface modification; TiO2 nanotubes; Osteogenic differentiation; Betal-integrin/Hedgehog-Gli1 signaling; Diameter

    Micro/nanotextured topographies (MNTs) can modulate cell-biomaterial interactions mostly by their controllable geometries. Among them, TiO2 nanotubes, regarded as having a highly controllable nanoscale geometry, have been extensively investigated and applied and significantly affect diameter-dependent cell biological behaviors. In this study, we used five typical MNTs decorated with TiO2 nanotubes with diameters of 30, 50, 70, 100 and 120 nm to explore the optimal nanotube diameter for improving the biofunctional properties and to more deeply understand the underlying mechanisms by which these MNTs affect osteogenic differentiation by revealing the effect of betal-integrin/Hedgehog-Glil signaling on this process. The MNTs affected MG63 osteoblast-like cell spreading, osteogenic gene expression (BMP-2, Runx2 and ALP), mineralization and ALP activity in a diameter-dependent pattern, and the optimal TiO2 nanotube diameter of 70 nm provided the best microenvironment for osteogenic differentiation as well as betal-integrin/Hedgehog-Gli1 signaling activation. This enhanced osteogenic differentiation by the optimal-diameter TiO2 nanotubes of 70 nm was attenuated via suppression of the betal-integrin/Hedgehog-Gli1 signaling, which indicated a significant role of this pathway in mediating the diameter-dependent osteogenic differentiation promotional effect of MNTs with different TiO2 nanotube diameters. These results might provide deeper insights into the signal transduction mechanisms by which different nanoscale geometries influence cellular functions for biomaterial modification and biofunctionalization.
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