The nanoscale geometry of TiO2 nanotubes influences the osteogenic differentiation of human adipose-derived stem cells by modulating H3K4 trimethylation |
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Institution: | 1. Jožef Stefan Institute, Jamova cesta 39, Ljubljana SI-1000, Slovenia;2. Laboratory of Biophysics, Faculty of Electrical Engineering, University of Ljubljana, Tržaška 25, Ljubljana SI-1000, Slovenia;3. Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia;4. Department of Materials Science and Engineering, WW4-LKO, University of Erlangen Nuremberg, Martensstr. 7, 91058 Erlangen, Germany;5. Centre of Polymer Systems, University Institute, Tomas Bata University in Zlin, Nad Ovcirnou 3685, 760 01 Zlin, Czech Republic;1. School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China;2. Tianjin Key Laboratory of Composite and Functional Materials, Tianjin 300072, China;3. School of Laboratory Medicine, Tianjin Medical University, Tianjin, 300203, China;1. Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China;2. School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China;3. School of Life Science, Chongqing University, Chongqing 400044, China;4. Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China |
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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 (TiO2) nanotube arrays of different diameters. Both in vitro and in vivo studies demonstrated that the nanoscale geometry influenced cellular differentiation and TiO2 nanotubes with a diameter of 70 nm was the optimal dimension for the osteogenic differentiation of hASCs. Moreover, we observed that TiO2 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. |
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Keywords: | Titanium Nanotubes Adipose-derived stem cells Osteogenic differentiation Bone tissue engineering Epigenetics |
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