Characterisation of miRNA Expression in Dental Pulp Cells during Epigenetically-Driven Reparative Processes

Michaela Kearney, Paul R. Cooper, Anthony J. Smith, Henry F. Duncan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Within regenerative endodontics, exciting opportunities exist for the development of next-generation targeted biomaterials that harness epigenetic machinery, including microRNAs (miRNAs), histone acetylation, and DNA methylation, which are used to control pulpitis and to stimulate repair. Although histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) induce mineralisation in dental pulp cell (DPC) populations, their interaction with miRNAs during DPC mineralisation is not known. Here, small RNA sequencing and bioinformatic analysis were used to establish a miRNA expression profile for mineralising DPCs in culture. Additionally, the effects of a HDACi, suberoylanilide hydroxamic acid (SAHA), and a DNMTi, 5-aza-2′-deoxycytidine (5-AZA-CdR), on miRNA expression, as well as DPC mineralisation and proliferation, were analysed. Both inhibitors increased mineralisation. However, they reduced cell growth. Epigenetically-enhanced mineralisation was accompanied by widespread changes in miRNA expression. Bioinformatic analysis identified many differentially expressed mature miRNAs that were suggested to have roles in mineralisation and stem cell differentiation, including regulation of the Wnt and MAPK pathways. Selected candidate miRNAs were demonstrated by qRT-PCR to be differentially regulated at various time points in mineralising DPC cultures treated with SAHA or 5-AZA-CdR. These data validated the RNA sequencing analysis and highlighted an increased and dynamic interaction between miRNA and epigenetic modifiers during the DPC reparative processes.
Original languageEnglish
Article number8631
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume24
Issue number10
DOIs
Publication statusPublished - 11 May 2023

Keywords

  • RNA sequencing
  • DNA methyltransferase inhibitor
  • vital pulp treatment
  • non-coding RNA
  • histone deacetylase inhibitor
  • dental pulp stem cells
  • epigenetics
  • microRNA

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