JARID1B represses the osteogenic potential of human periodontal ligament mesenchymal cells

Oral Dis. 2024 Sep;30(6):3971-3981. doi: 10.1111/odi.14814. Epub 2023 Nov 22.

Abstract

Background: Here, we evaluated whether the histone lysine demethylase 5B (JARID1B), is involved in osteogenic phenotype commitment of periodontal ligament cells (PDLCs), by considering their heterogeneity for osteoblast differentiation.

Materials and methods: Epigenetic, transcriptional, and protein levels of a gene set, involved in the osteogenesis, were investigated by performing genome-wide DNA (hydroxy)methylation, mRNA expression, and western blotting analysis at basal (without osteogenic induction), and at the 3rd and 10th days of osteogenic stimulus, in vitro, using PDLCs with low (l) and high (h) osteogenic potential as biological models.

Results: h-PDLCs showed reduced levels of JARID1B, compared to l-PDLCs, with significant inversely proportional correlations between RUNX2 and RUNX2/p57. Epigenetically, a significant reduction in the global H3K4me3 content was observed only in h-PDLCs. Immunoblotting data reveal a significant reduction in the global H3K4me3 content, at 3 days of induction only in h-PDLCs, while an increase in the global H3K4me3 content was observed at 10 days for both PDLCs. Additionally, positive correlations were found between global H3K4me3 levels and JARID1B gene expression.

Conclusions: Altogether, our results show the crucial role of JARID1B in repressing PDLCs osteogenic phenotype and this claims to pre-clinical protocols proposing JARID1B as a potential therapeutic target.

Keywords: JARID1B; PDLC; bone; epigenetics; mesenchymal stem cells; osteoblast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cell Differentiation
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit* / metabolism
  • DNA Methylation
  • Epigenesis, Genetic
  • Histones / metabolism
  • Humans
  • Jumonji Domain-Containing Histone Demethylases* / genetics
  • Jumonji Domain-Containing Histone Demethylases* / metabolism
  • Mesenchymal Stem Cells* / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Osteogenesis* / genetics
  • Periodontal Ligament* / cytology
  • Periodontal Ligament* / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism

Substances

  • Jumonji Domain-Containing Histone Demethylases
  • Core Binding Factor Alpha 1 Subunit
  • RUNX2 protein, human
  • KDM5B protein, human
  • Repressor Proteins
  • Histones
  • Nuclear Proteins
  • histone H3 trimethyl Lys4