Epigenetic pathways regulating bone homeostasis:Potential targeting for intervention of skeletal disorders

Jonathan A.R. Gordon, Martin A. Montecino, Rami I. Aqeilan, Janet L. Stein, Gary S. Stein, Jane B. Lian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Epigenetic regulation utilizes different mechanisms to convey heritable traits to progeny cells that are independent of DNA sequence, including DNA silencing, posttranslational modifications of histone proteins, and the posttranscriptional modulation of RNA transcript levels by noncoding RNAs.Although long non-coding RNAs have recently emerged as important regulators of gene imprinting, their functions during osteogenesis are as yet unexplored.In contrast, microRNAs (miRNAs) are well characterized for their control of osteogenic and osteoclastic pathways; thus, further defining how gene regulatory networks essential for skeleton functions are coordinated and finely tuned through the activities of miRNAs.Roles of miRNAs are constantly expanding as new studies uncover associations with skeletal disorders.The distinct functions of epigenetic regulators and evidence for integrating their activities to control normal bone gene expression and bone disease will be presented.In addition, potential for using “signature miRNAs” to identify, manage, and therapeutically treat osteosarcoma will be discussed in this review.

Original languageAmerican English
Pages (from-to)496-506
Number of pages11
JournalCurrent Osteoporosis Reports
Volume12
Issue number4
DOIs
StatePublished - 1 Nov 2014

Bibliographical note

Funding Information:
Acknowledgements We thank Jennifer Díaz for manuscript preparation and formatting, and S. H. Ralston of the Molecular Medicine Centre and Western General Hospital (Edinburgh, UK) and M. L. Johnson of the University of Missouri (Kansas City, USA) for their review of the manuscript. The authors acknowledge financial support from the National Institutes of Health (National Cancer Institute P01 CA082834, National Institute of Dental and Craniofacial Research R37 DE012528, National Institute of Arthritis and Musculoskeletal and Skin Diseases R01 AR039588 and P01 AR048818), and the US-Israel Binational Science Foundation (2011300), and FONDAP 15090007.

Publisher Copyright:
© Springer Science+Business Media New York 2014.

Keywords

  • DNAmethylation
  • Epigenetic marks in bone
  • Histonemodifications
  • Osteoblast regulation
  • Osteosarcoma miRNAs
  • miRNA

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