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The epigenetic mechanisms of nanotopography-guided osteogenic differentiation of mesenchymal stem cells via high-throughput transcriptome sequencing

Authors Lv L, Liu Y, Zhang P, Bai X, Ma X, Wang Y, Li H, Wang L, Zhou Y

Received 22 March 2018

Accepted for publication 29 June 2018

Published 20 September 2018 Volume 2018:13 Pages 5605—5623

DOI https://doi.org/10.2147/IJN.S168928

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Longwei Lv,1 Yunsong Liu,1 Ping Zhang,1 Xiangsong Bai,1 Xiaohan Ma,1 Yuejun Wang,1 Hongyi Li,2 Li Wang,3 Yongsheng Zhou1

1Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Disease, Beijing Key Laboratory of Digital Stomatology, Beijing, People’s Republic of China; 2The key Laboratory of Advanced Functional Materials, Ministry of Education of China, College of Materials Science and Engineering, Beijing University of Technology, Beijing 100124, China; 3State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, People’s Republic of China

Background:
Nanotopography directs stem cell fate; however, the underlying mechanisms, especially those at the epigenetic level, remain vague. The TiO2-nanotube array, a classical example of nanotopography, is a good model to investigate topography–cell interactions because of its good controllability and easy manufacturing process. Previously, we found that a TiO2-nanotube array with an optimal diameter promoted osteogenic differentiation of human adipose-tissue-derived stem cells (hASCs).
Methods: We used RNA sequencing and bioinformatics to reveal the overall gene expression profile of hASCs on TiO2-nanotube arrays.
Results: Bioinformatics analyses revealed that the epigenetic regulatory network plays an important role in TiO2-nanotube-guided osteogenic differentiation. Changes in cell adhesion and cytoskeletal reorganization are linked to epigenetic alterations, including upregulation of KDM4E and downregulation of histone deacetylases. Meanwhile, microRNAs, including miR-24-1-5p, miR-24–3 p, miR-154–3 p, miR-154–5 p, miR-433–5 p, miR-589–3 p, and miR-589–5 p were downregulated, whereas miR-186–5 p and miR-770–5 p were upregulated. Long non-coding RNAs, including LINC00941, LINC01279, and ZFAS1, were downregulated in this process.
Conclusion: Using next-generation sequencing, we illustrated the overall picture of the regulatory mechanisms of TiO2 nanotubes, thus providing a basis for future clinical applications of nanotopography in the field of bone tissue engineering. Our results offer insights into material-based nanomedicine and epigenetic therapy.

Keywords: TiO2 nanotubes, RNA sequencing, osteogenic differentiation, epigenetics, histone modification, non-coding RNA

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