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The nanoscale geometry of TiO2 nanotubes influences the osteogenic differentiation of human adipose-derived stem cells by modulating H3K4 trimethylation
Biomaterials, Issue: , Volume: 39, Pages: 193-205. | 2015-01-01
0 Patent citations    45 Scholarly citations     Reference Count: 50
Longwei Lv;Yunsong Liu;Ping Zhang;Xiao Zhang;Jianzhang Liu;Tong Chen;Penglei Su;Hongyi Li;Yongsheng Zhou

摘要

Abstract Nanostructured materials can direct stem cell lineage commitment solely by their various, but controllable, geometric cues, which would be very important for their future application in bone tissue engineering and bone regeneration. However, the mechanisms by which nano-geometric cues dictate the osteogenic differentiation of stem cells remain unclear. Epigenetics is central to cellular differentiation, a process that regulates heritable and long-lasting alterations in gene expression without changing the DNA sequence. Here, we explored the varied osteogenic behaviors of human adipose-derived stem cells (hASCs) on titanium dioxide (TiO 2 ) nanotube arrays of different diameters. Both in vitro and in vivo studies demonstrated that the nanoscale geometry influenced cellular differentiation and TiO 2 nanotubes with a diameter of 70 nm was the optimal dimension for the osteogenic differentiation of hASCs. Moreover, we observed that TiO 2 nanotubes promoted the osteogenic differentiation of hASCs by upregulating methylation level of histone H3 at lysine 4 (H3K4) in the promoter regions of osteogenic genes Runx2 and osteocalcin, by inhibiting demethylase retinoblastoma binding protein 2 (RBP2). These results revealed, for the first time, the epigenetic mechanism by which nanotopography directs stem cell fate.


机构

Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China.Beijing University of Technology;Photoelectrochemical Research Group, School of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, China.Beijing University of Technology;Photoelectrochemical Research Group, School of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, China. Electronic address: lhy06@bjut.edu.cn.Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China; National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China. Electronic address: kqzhouysh@hsc.pku.edu.cn.


实验动物:

mouse(小鼠)   

科学仪器:

Chip System(芯片系统)   

细胞器官:

adipose-derived stem cell   

方法技术:

embryotoxicity test    gene transfection    angiography   

基因:

Runx2 gene    Osteocalcin gene   

实验试剂:

Titanium(D014025)    titanium dioxide(C009495)   

免疫治疗:

Molecular biology    Cellular differentiation    Materials Science    Epigenetics   

文献类型:

journal article;research support, non-u.s. gov't;

出版商:

Elsevier BV

发表时间:

2015-01-01

基金信息

National Health and Family Planning Commission of China (2011)()