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Epigenetic Pathways Regulating Bone Homeostasis: Potential Targeting for Intervention of Skeletal Disorders

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Abstract

Epigenetic regulation utilizes different mechanisms to convey heritable traits to progeny cells that are independent of DNA sequence, including DNA silencing, post-translational modifications of histone proteins, and the post-transcriptional modulation of RNA transcript levels by non-coding 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.

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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.

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Conflict of Interest

J. A. R. Gordon, M. A. Montecino, R. I. Aqeilan, J. L. Stein, G. S. Stein, and J. B. Lian declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

All studies by the authors involving animal and/or human subjects were performed after approval by the appropriate institutional review boards. When required, written informed consent was obtained from all participants.

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Authors and Affiliations

  1. Department of Biochemistry and Vermont Cancer Center, University of Vermont College of Medicine, 89 Beaumont Avenue, Burlington, VT, USA

    Jonathan A. R. Gordon, Janet L. Stein, Gary S. Stein & Jane B. Lian

  2. Centro de Investigaciones Biomedicas and FONDAP Center for Genome Regulation, Universidad Andres Bello, Avenida Republica 239, Santiago, Chile

    Martin A. Montecino

  3. Lautenberg Center for Immunology and Cancer Research-IMRIC, Hebrew University-Hadassah Medical School, PO Box 12272, Ein Karem Campus, Jerusalem, 91120, Israel

    Rami I. Aqeilan

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  1. Jonathan A. R. Gordon
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  4. Janet L. Stein
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Correspondence to Jane B. Lian.

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Gordon, J.A.R., Montecino, M.A., Aqeilan, R.I. et al. Epigenetic Pathways Regulating Bone Homeostasis: Potential Targeting for Intervention of Skeletal Disorders. Curr Osteoporos Rep 12, 496–506 (2014). https://doi.org/10.1007/s11914-014-0240-1

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