Man, K, Lawlor, L, Jiang, LH orcid.org/0000-0001-6398-0411 et al. (1 more author) (2021) The selective histone deacetylase inhibitor mi192 enhances the osteogenic differentiation efficacy of human dental pulp stromal cells. International Journal of Molecular Sciences, 22 (10). ISSN 1661-6596
Abstract
The use of human dental pulp stromal cells (hDPSCs) has gained increasing attention as an alternative stem cell source for bone tissue engineering. The modification of the cells’ epigenetics has been found to play an important role in regulating differentiation, with the inhibition of histone deacetylases 3 (HDAC3) being linked to increased osteogenic differentiation. This study aimed to induce epigenetic reprogramming using the HDAC2 and 3 selective inhibitor, MI192 to promote hDPSCs osteogenic capacity for bone regeneration. MI192 treatment caused a time–dose-dependent change in hDPSC morphology and reduction in viability. Additionally, MI192 successfully aug-mented hDPSC epigenetic functionality, which resulted in increased histone acetylation and cell cycle arrest at the G2/M phase. MI192 pre-treatment exhibited a dose-dependent effect on hDPSCs alkaline phosphatase activity. Quantitative PCR and In-Cell Western further demonstrated that MI192 pre-treatment significantly upregulated hDPSCs osteoblast-related gene and protein expression (alkaline phosphatase, bone morphogenic protein 2, type I collagen and osteocalcin) during osteogenic differentiation. Importantly, MI192 pre-treatment significantly increased hDPSCs extracellular matrix collagen production and mineralisation. As such, for the first time, our findings show that epigenetic reprogramming with the HDAC2 and 3 selective inhibitor MI192 accelerates the os-teogenic differentiation of hDPSCs, demonstrating the considerable utility of this MSCs engineering approach for bone augmentation strategies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) |
Keywords: | histone deacetylase; HDAC inhibitor; epigenetics; MI192; bone tissue engineering; human dental pulp stromal cells |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Biology (Leeds) |
Funding Information: | Funder Grant number EU - European Union 318553 |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 May 2021 11:00 |
Last Modified: | 26 May 2021 11:00 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/ijms22105224 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:174527 |