Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases

Int J Mol Sci. 2022 Jan 28;23(3):1500. doi: 10.3390/ijms23031500.

Abstract

Bone metabolism consists of a balance between bone formation and bone resorption, which is mediated by osteoblast and osteoclast activity, respectively. In order to ensure bone plasticity, the bone remodeling process needs to function properly. Mesenchymal stem cells differentiate into the osteoblast lineage by activating different signaling pathways, including transforming growth factor β (TGF-β)/bone morphogenic protein (BMP) and the Wingless/Int-1 (Wnt)/β-catenin pathways. Recent data indicate that bone remodeling processes are also epigenetically regulated by DNA methylation, histone post-translational modifications, and non-coding RNA expressions, such as micro-RNAs, long non-coding RNAs, and circular RNAs. Mutations and dysfunctions in pathways regulating the osteoblast differentiation might influence the bone remodeling process, ultimately leading to a large variety of metabolic bone diseases. In this review, we aim to summarize and describe the genetics and epigenetics of the bone remodeling process. Moreover, the current findings behind the genetics of metabolic bone diseases are also reported.

Keywords: DNA methylation; bone disease; bone formation; bone morphogenic protein; bone remodeling; histone post-translational modifications; long non-coding RNA; metabolic bone disease; microRNA; non-coding RNA; osteogenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Diseases, Metabolic / genetics*
  • Bone Remodeling
  • DNA Methylation
  • Epigenesis, Genetic*
  • Genetic Predisposition to Disease / genetics*
  • Histone Code
  • Humans
  • Osteogenesis
  • RNA, Untranslated / genetics
  • Wnt Signaling Pathway

Substances

  • RNA, Untranslated