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

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.

Biomaterial Cues Regulate Epigenetic State and Cell Functions-A Systematic Review.

Biomaterial cues can act as potent regulators of cell niche and microenvironment. Epigenetic regulation plays an important role in cell functions, including proliferation, differentiation, and reprogramming. It is now well appreciated that biomaterials can alter epigenetic states of cells. In this study, we systematically reviewed the underlying epigenetic mechanisms of how different biomaterial cues, including material chemistry, topography, elasticity, and mechanical stimulus, influence cell functions, such as nuclear deformation, cell proliferation, differentiation, and reprogramming, to summarize the differences and similarities among each biomaterial cues and their mechanisms, and to find common and unique properties of different biomaterial cues. Moreover, this work aims to establish a mechanogenomic map facilitating highly functionalized biomaterial design, and renders new thoughts of epigenetic regulation in controlling cell fates in disease treatment and regenerative medicine.