Epigenetic Control of Osteogenesis: Pathways Toward Improved Bone Regeneration

Curr Osteoporos Rep. 2025 Jun 18;23(1):27. doi: 10.1007/s11914-025-00923-4.

Abstract

Purpose of review: In this review, we summarize our evolving understanding of the epigenetic mechanisms directing the osteogenic differentiation of skeletal progenitor cells.

Recent findings: Advances in genome-wide approaches used to profile chromatin accessibility and histone modifications in skeletal progenitors have uncovered chromatin remodeling associated with progression of osteoblast differentiation and the key regulatory nodes driving this process. Utilization of cell culture systems and genetic mouse models highlight the key enzymes regulating histone posttranslational modifications and DNA methylation that promote the transition of cells from progenitor to mature osteoblast stage. Herein, the described studies provide emerging insights gained from pharmacologic targeting of chromatin modifiers promoting osteogenic differentiation of skeletal progenitors. While our fundamental understanding of chromatin modifiers and factors regulating chromatin accessibility and transcriptional activity in skeletal progenitors continues to develop, future research may inform new therapeutic approaches to promote osteoblast differentiation and enhance mineralization to augment fracture repair.

Keywords: Chromatin modifying enzymes; Epigenetic regulation; Fracture; Osteogenic differentiation; Skeletal stem and progenitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Regeneration* / genetics
  • Cell Differentiation / genetics
  • Chromatin Assembly and Disassembly
  • DNA Methylation
  • Epigenesis, Genetic*
  • Histones / metabolism
  • Humans
  • Mice
  • Osteoblasts* / cytology
  • Osteoblasts* / metabolism
  • Osteogenesis* / genetics

Substances

  • Histones