Epigenetics and Bone Remodeling
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Purpose of Review
Bone remodeling is a diverse field of study with many direct clinical applications; past studies have implicated epigenetic alterations as key factors of both normal bone tissue development and function and diseases of pathologic bone remodeling. The purpose of this article is to review the most important recent advances that link epigenetic changes to the bone remodeling field.
Epigenetics describes three major phenomena: DNA modification via methylation, histone side chain modifications, and short non-coding RNA sequences which work in concert to regulate gene transcription in a heritable fashion. Recent findings include the role of DNA methylation changes of Wnt, RANK/RANKL, and other key signaling pathways, epigenetic regulation of osteoblast and osteoclast differentiation, and others.
Although much work has been done, much is still unknown. Future epigenome-wide studies should focus on extending the tissue coverage, integrating multiple epigenetic analyses with transcriptome data, and working to uncover epigenetic changes linked with early events in aberrant bone remodeling.
KeywordsBone remodeling Epigenetics DNA methylation Histone modification miRNA Review
Compliance with Ethical Standards
Conflict of Interest
Matlock Jeffries and Ali Husain declare no conflicts of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
- 13.Jeffries MA, Donica M, Baker L, Stevenson M, Annan AC, Humphrey MB, et al. Genome-wide DNA methylation study identifies significant epigenomic changes in osteoarthritic subchondral bone and similarity to overlying cartilage. Arthritis Rheumatol. 2015; Available from: doi: 10.1002/art.39555.
- 25.Gong Y E et al. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. 2017. - PubMed - NCBI [Internet]. [cited 2017 Jan 22]. Available from: https://connect.omrf.org/pubmed/,DanaInfo=www.ncbi.nlm.nih.gov,SSL+11719191.
- 39.•• Reppe S, Noer A, Grimholt RM, Halldórsson BV, Medina-Gomez C, Gautvik VT, et al. Methylation of bone SOST, its mRNA, and serum sclerostin levels correlate strongly with fracture risk in postmenopausal women. J Bone Miner Res. 2015;30:249–56. One of the only studies in this field to examine DNA methylation changes in a particular tissue (bone) with overall risk of a systemic bone remodeling disorder (osteoporosis).CrossRefPubMedGoogle Scholar
- 40.•• Lhaneche L, Hald JD, Domingues A, Hannouche D, Delepine M, Zelenika D, et al. Variations of SOST mRNA expression in human bone are associated with DNA polymorphism and DNA methylation in the SOST gene. Bone. 2016;92:107–15. A good example of how genetics and epigenetics interact to influence gene expression related to bone remodeling.CrossRefPubMedGoogle Scholar
- 42.Chiba N, Furukawa K-I, Takayama S, Asari T, Chin S, Harada Y, et al. Decreased DNA methylation in the promoter region of the WNT5A and GDNF genes may promote the osteogenicity of mesenchymal stem cells from patients with ossified spinal ligaments. J Pharmacol Sci. 2015;127:467–73.CrossRefPubMedGoogle Scholar
- 49.Reppe S, Grimholt RM, Lyle R, Olstad OK, Gautvik VT, Gautvik KM. Strong correlation between BMD associated transcripts in postmenopausal iliac bone biopsies and DNA methylation levels at specific CpGs. J Bone Miner Res. 2014;S74. WILEY-BLACKWELL 111 RIVER ST, HOBOKEN 07030-5774, NJ USA.Google Scholar
- 50.Reppe S E et al. The influence of DNA methylation on bone cells. - PubMed - NCBI [Internet]. 2015 [cited 2017 Jan 18]. Available from: https://connect.omrf.org/pubmed/,DanaInfo=www.ncbi.nlm.nih.gov,SSL+?term=The+Influence+of+DNA+Methylation+on+Bone+Cells.
- 51.Del Real A, Pérez-Campo FM, Fernández AF, Sañudo C, Ibarbia CG, Pérez-Núñez MI, et al. Differential analysis of genome-wide methylation and gene expression in mesenchymal stem cells of patients with fractures and osteoarthritis. Epigenetics. 2016:1–10.Google Scholar
- 54.Holzer LA. Subchondral bone: an emerging target for treatment of osteoarthritis. J Rheum Dis Treat. 2015;1. Available from: https://clinmedjournals.org/articles/jrdt/jrdt-1-001e.php?jid=jrdt.
- 61.Qin H-T, Li H-Q, Liu F. Selective histone deacetylase small molecule inhibitors: recent progress and perspectives. Expert Opin Ther Pat. 2016;1–15.Google Scholar
- 81.Gaur T, Hussain S, Mudhasani R, Parulkar I, Colby JL, Frederick D, et al. Dicer inactivation in osteoprogenitor cells compromises fetal survival and bone formation, while excision in differentiated osteoblasts increases bone mass in the adult mouse. Dev Biol. 2010;340:10–21.CrossRefPubMedPubMedCentralGoogle Scholar
- 92.•• Seeliger C, Karpinski K, Haug AT, Vester H, Schmitt A, Bauer JS, et al. Five freely circulating miRNAs and bone tissue miRNAs are associated with osteoporotic fractures. J Bone Miner Res. 2014;29:1718–28. A well-done study demonstrating the potential of serum epigenetic patterns as diagnostic biomarkers in clinical osteoporosis.CrossRefPubMedGoogle Scholar