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Int. J. Mol. Sci. 2016, 17(8), 1329; doi:10.3390/ijms17081329

Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

Department of Surgery and Translational Medicine, University of Florence and Metabolic Bone Diseases Unit, University Hospital of Florence, Largo Palagi 1, 50139 Florence, Italy
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Academic Editor: William Chi-shing Cho
Received: 1 July 2016 / Revised: 27 July 2016 / Accepted: 5 August 2016 / Published: 12 August 2016
(This article belongs to the Special Issue Precision Medicine—From Bench to Bedside)
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Abstract

Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles. View Full-Text
Keywords: gene expression; histone modifications; DNA methylation; microRNAs; precision medicine; fragility fracture gene expression; histone modifications; DNA methylation; microRNAs; precision medicine; fragility fracture
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Marini, F.; Cianferotti, L.; Brandi, M.L. Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices? Int. J. Mol. Sci. 2016, 17, 1329.

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