Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells

Micro/nano topological modification is critical for improving the in vivo behaviors of bone implants, regulating multiple cellular functions. Titania (TiO2) nanotubes show the capacity of promoting osteoblast-related cell differentiation and induce effective osseointegration, serving as a model mate...

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Main Authors: Li Jinsheng, Deng Qing, Chen Junhao, Si Qiqi, Chen Jieru, Yang Liwen, Guo Zhiyun, Guo Tailin, Weng Jie
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:SLAS Discovery
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2472555223001120
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author Li Jinsheng
Deng Qing
Chen Junhao
Si Qiqi
Chen Jieru
Yang Liwen
Guo Zhiyun
Guo Tailin
Weng Jie
author_facet Li Jinsheng
Deng Qing
Chen Junhao
Si Qiqi
Chen Jieru
Yang Liwen
Guo Zhiyun
Guo Tailin
Weng Jie
author_sort Li Jinsheng
collection DOAJ
description Micro/nano topological modification is critical for improving the in vivo behaviors of bone implants, regulating multiple cellular functions. Titania (TiO2) nanotubes show the capacity of promoting osteoblast-related cell differentiation and induce effective osseointegration, serving as a model material for studying the effects of micro/nano-topological modifications on cells. However, the intracellular signaling pathways by which TiO2 nanotubes regulate the osteogenic differentiation of stem cells are not fully defined. Thy-1 (CD90), a cell surface glycoprotein anchored by glycosylphosphatidylinositol, has been considered a key molecule in osteoblast differentiation in recent years. Nevertheless, whether the micro/nano topology of the implant surface leads to changes in Thy-1 is unknown, as well as whether these changes promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, TiO2 nanotubes of various diameters were prepared by adjusting the anodizing voltage. qPCR and immunoblot were carried out to assess the mechanism by which TiO2 nanotubes regulate Thy-1. The results revealed Ti plates harboring TiO2 nanotubes ∼100-nm diameter (TNT-100) markedly upregulated Thy-1. Subsequently, upregulated Thy-1 promoted the activation of Fyn/RhoA/MLC Ⅱ/F-actin axis, which enhanced the nuclear translocation of YAP. After Thy-1 knockdown by siRNA, the Fyn/RhoA/MLC Ⅱ/F-actin axis was significantly inhibited and TiO2 nanotubes showed decreased effects on osteogenic differentiation. Therefore, Thy-1 upregulation might be a major mechanism by which micro/nano-topological modification of TiO2 nanotubes promotes osteogenic differentiation in BMSCs. This study provides novel insights into the molecular mechanism of TiO2 nanotubes, which may help design improved bone implants for clinical application.
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spelling doaj.art-7695897422a241e7891957f95d094f7d2024-03-29T05:50:59ZengElsevierSLAS Discovery2472-55522024-04-01293100139Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cellsLi Jinsheng0Deng Qing1Chen Junhao2Si Qiqi3Chen Jieru4Yang Liwen5Guo Zhiyun6Guo Tailin7Weng Jie8Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China; Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR ChinaInstitute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, ChinaSchool of Finance and Economics, Xizang Minzu University, Xianyang 712082, PR ChinaSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ChinaSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ChinaInstitute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China; Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR ChinaSchool of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, ChinaInstitute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China; Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China; Corresponding authors.Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan, China; Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China; Corresponding authors.Micro/nano topological modification is critical for improving the in vivo behaviors of bone implants, regulating multiple cellular functions. Titania (TiO2) nanotubes show the capacity of promoting osteoblast-related cell differentiation and induce effective osseointegration, serving as a model material for studying the effects of micro/nano-topological modifications on cells. However, the intracellular signaling pathways by which TiO2 nanotubes regulate the osteogenic differentiation of stem cells are not fully defined. Thy-1 (CD90), a cell surface glycoprotein anchored by glycosylphosphatidylinositol, has been considered a key molecule in osteoblast differentiation in recent years. Nevertheless, whether the micro/nano topology of the implant surface leads to changes in Thy-1 is unknown, as well as whether these changes promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Here, TiO2 nanotubes of various diameters were prepared by adjusting the anodizing voltage. qPCR and immunoblot were carried out to assess the mechanism by which TiO2 nanotubes regulate Thy-1. The results revealed Ti plates harboring TiO2 nanotubes ∼100-nm diameter (TNT-100) markedly upregulated Thy-1. Subsequently, upregulated Thy-1 promoted the activation of Fyn/RhoA/MLC Ⅱ/F-actin axis, which enhanced the nuclear translocation of YAP. After Thy-1 knockdown by siRNA, the Fyn/RhoA/MLC Ⅱ/F-actin axis was significantly inhibited and TiO2 nanotubes showed decreased effects on osteogenic differentiation. Therefore, Thy-1 upregulation might be a major mechanism by which micro/nano-topological modification of TiO2 nanotubes promotes osteogenic differentiation in BMSCs. This study provides novel insights into the molecular mechanism of TiO2 nanotubes, which may help design improved bone implants for clinical application.http://www.sciencedirect.com/science/article/pii/S2472555223001120Micro/nano-topologyTiO2 nanotubeThy-1FynOsteogenic differentiation
spellingShingle Li Jinsheng
Deng Qing
Chen Junhao
Si Qiqi
Chen Jieru
Yang Liwen
Guo Zhiyun
Guo Tailin
Weng Jie
Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells
SLAS Discovery
Micro/nano-topology
TiO2 nanotube
Thy-1
Fyn
Osteogenic differentiation
title Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells
title_full Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells
title_fullStr Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells
title_full_unstemmed Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells
title_short Micro/nano topological modification of TiO2 nanotubes activates Thy-1 signaling to control osteogenic differentiation of stem cells
title_sort micro nano topological modification of tio2 nanotubes activates thy 1 signaling to control osteogenic differentiation of stem cells
topic Micro/nano-topology
TiO2 nanotube
Thy-1
Fyn
Osteogenic differentiation
url http://www.sciencedirect.com/science/article/pii/S2472555223001120
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