Skip to main content

Advertisement

SpringerLink
Log in

Regulation of Bone Metabolism by microRNAs

  • Genetics (M Johnson and S Ralston, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The small non-coding microRNAs (miRNAs) have emerged as important post-transcriptional regulators of various physiological and pathological processes. The purpose of this article is to review the important recent advances on the role of miRNAs in bone remodeling and metabolic bone disorders.

Recent Findings

In a physiological context, miRNAs regulate bone formation and bone resorption, thereby contributing to the maintenance of bone homeostasis. Under pathological conditions, an aberrant miRNA signaling contributes to the onset and progression of skeletal disorders, such as osteoporosis. Furthermore, miRNAs can be secreted to circulation and have clinical potential as non-invasive biomarkers. In a therapeutic setting, miRNA delivery or antagonism has been reported to affect several diseases under pre-clinical conditions thereby emerging as novel pharmacological tools.

Summary

miRNAs are key regulators of bone remodeling in health and disease. The future perspectives in the field include the role of secreted miRNAs in cell-cell communication in the bone environment. Furthermore, the clinical potential of using miRNAs as diagnostic tools and therapeutic targets to treat metabolic bone diseases provides an attractive future direction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Baron R, Hesse E. Update on bone anabolics in osteoporosis treatment: rationale, current status, and perspectives. J Clin Endocrinol Metab [Internet]. 2012 Feb [cited 2016 Apr 28];97(2):311–25. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3275361&tool=pmcentrez&rendertype=abstract.

  2. Harvey N, Dennison E, Cooper C. Osteoporosis: impact on health and economics. Nat Rev Rheumatol [Internet]. 2010 Feb [cited 2017 Oct 17];6(2):99–105. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20125177.

  3. Karasik D, Rivadeneira F, Johnson ML. The genetics of bone mass and susceptibility to bone diseases. Nat Rev Rheumatol [Internet]. 2016 Apr 7 [cited 2017 Oct 25];12(6):323–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27052486.

  4. Hassan MQ, Tye CE, Stein GS, Lian JB. Non-coding RNAs: epigenetic regulators of bone development and homeostasis. Bone [Internet]. 2015 Dec [cited 2017 Oct 16];81:746–56. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26039869.

  5. Bilezikian JP, Matsumoto T, Bellido T, Khosla S, Martin J, Recker RR, et al. Targeting bone remodeling for the treatment of osteoporosis: summary of the proceedings of an ASBMR workshop. J Bone Miner Res. 2009;24(3):373–85. https://doi.org/10.1359/jbmr.090105.

    Article  PubMed  Google Scholar 

  6. Mirza F, Canalis E. Management of endocrine disease: secondary osteoporosis: pathophysiology and management. Eur J Endocrinol [Internet]. 2015 Sep [cited 2017 Oct 17];173(3):R131–51. Available from: http://www.eje-online.org/lookup/doi/10.1530/EJE-15-0118

  7. Harvey N, Dennison E, Cooper C. Osteoporosis: impact on health and economics. Nat Rev Rheumatol. 2010;6(2):99–105. https://doi.org/10.1038/nrrheum.2009.260.

    Article  PubMed  Google Scholar 

  8. Harada S, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003;423(6937):349–55. https://doi.org/10.1038/nature01660.

    Article  CAS  PubMed  Google Scholar 

  9. Taipaleenmäki H, Bjerre Hokland L, Chen L, Kauppinen S, Kassem M. Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation. Eur J Endocrinol [Internet]. 2012 Mar [cited 2016 Apr 28];166(3):359–71. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22084154.

  10. Lian JB, Stein GS, van Wijnen AJ, Stein JL, Hassan MQ, Gaur T, et al. MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol [Internet]. 2012 Apr [cited 2016 Apr 28];8(4):212–27. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3589914&tool=pmcentrez&rendertype=abstract.

  11. van Wijnen AJ, van de Peppel J, van Leeuwen JP, Lian JB, Stein GS, Westendorf JJ, et al. MicroRNA functions in osteogenesis and dysfunctions in osteoporosis. Curr Osteoporos Rep [Internet]. 2013 Jun 23 [cited 2017 Oct 14];11(2):72–82. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23605904.

  12. • Gennari L, Bianciardi S, Merlotti D. MicroRNAs in bone diseases. Osteoporos Int [Internet]. 2017 Apr 30 [cited 2017 Oct 14];28(4):1191–213. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27904930. Recent, comprehensive review on the role of miRNAs in bone.

  13. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell [Internet]. 2005 Jan 14 [cited 2017 Oct 16];120(1):15–20. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15652477.

  14. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature [Internet]. 2005 Feb 17 [cited 2017 Oct 16];433(7027):769–73. Available from: http://www.nature.com/doifinder/10.1038/nature03315.

  15. Kozomara A, Griffiths-Jones S. miRBase: annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res [Internet]. 2014 Jan [cited 2017 Oct 16];42(D1):D68–73. Available from: https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkt1181.

  16. Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res [Internet]. 2009 Jan 29 [cited 2017 Oct 16];19(1):92–105. Available from: http://genome.cshlp.org/cgi/doi/10.1101/gr.082701.108

  17. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res [Internet]. 2005 Nov 27 [cited 2017 Oct 16];33(20):e179–e179. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16314309.

  18. Hassan MQ, Gordon JAR, Beloti MM, Croce CM, Wijnen AJV, Stein JL, et al. A network connecting Runx2, SATB2, and the miR-23a 27a 24-2 cluster regulates the osteoblast differentiation program. Proc Natl Acad Sci [Internet]. 2010 Nov 16 [cited 2017 Oct 16];107(46):19879–84. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20980664.

  19. Hassan MQ, Maeda Y, Taipaleenmaki H, Zhang W, Jafferji M, Gordon JAR, et al. miR-218 directs a Wnt signaling circuit to promote differentiation of osteoblasts and osteomimicry of metastatic cancer cells. J Biol Chem [Internet]. 2012 Dec 7 [cited 2017 Oct 16];287(50):42084–92. Available from: http://www.jbc.org/lookup/doi/10.1074/jbc.M112.377515

  20. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science (80- ) [Internet]. 2001 Oct 26 [cited 2017 Oct 16];294(5543):853–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11679670.

  21. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science (80- ) [Internet]. 2001 Oct 26 [cited 2017 Oct 16];294(5543):858–62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11679671.

  22. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol [Internet]. 2009 Mar [cited 2017 Oct 16];11(3):228–34. Available from: http://www.nature.com/doifinder/10.1038/ncb0309-228

  23. Denli AM, Tops BBJ, Plasterk RHA, Ketting RF, Hannon GJ. Processing of primary microRNAs by the Microprocessor complex. Nature [Internet]. 2004 Nov 11 [cited 2017 Oct 16];432(7014):231–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15531879.

  24. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature [Internet]. 2003 Sep 25 [cited 2017 Oct 16];425(6956):415–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14508493.

  25. Marco A, Macpherson JI, Ronshaugen M, Griffiths-Jones S. MicroRNAs from the same precursor have different targeting properties. Silence [Internet]. 2012 Sep 27 [cited 2017 Oct 17];3(1):8. Available from: http://silencejournal.biomedcentral.com/articles/10.1186/1758-907X-3-8

  26. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell [Internet]. 2009 Jan 23 [cited 2017 Oct 16];136(2):215–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19167326.

  27. Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, Basyuk E, et al. Inhibition of translational initiation by Let-7 microRNA in human cells. Science (80- ) [Internet]. 2005 Sep 2 [cited 2017 Oct 17];309(5740):1573–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16081698.

  28. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol [Internet]. 2007 Jun 7 [cited 2017 Oct 17];9(6):654–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17486113.

  29. Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol [Internet]. 2011 Apr 20 [cited 2017 Oct 17];13(4):423–33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21423178.

  30. Wang K, Zhang S, Weber J, Baxter D, Galas DJ. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res [Internet]. 2010 Nov [cited 2017 Oct 17];38(20):7248–59. Available from: https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkq601

  31. Chen X, Liang H, Zhang J, Zen K, Zhang C-Y. Secreted microRNAs: a new form of intercellular communication. Trends Cell Biol [Internet]. 2012 Mar [cited 2017 Oct 17];22(3):125–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22260888.

  32. Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem [Internet]. 2010 Nov 1 [cited 2017 Oct 17];56(11):1733–41. Available from: http://www.clinchem.org/cgi/doi/10.1373/clinchem.2010.147405

  33. • Hackl M, Heilmeier U, Weilner S, Grillari J. Circulating microRNAs as novel biomarkers for bone diseases—complex signatures for multifactorial diseases? Mol Cell Endocrinol [Internet]. 2016 Sep 5 [cited 2017 Oct 14];432:83–95. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26525415. Review highlighting the role of circulating miRNAs as potential biomarkers in bone disaeses.

  34. Compston J. Osteoporosis: advances in risk assessment and management. Clin Med (Northfield Il) [Internet]. 2016 Dec 1 [cited 2017 Oct 17];16(Suppl_6):s121–4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27956452.

  35. Silverman SL, Calderon AD. The utility and limitations of FRAX: a US perspective. Curr Osteoporos Rep [Internet]. 2010 Dec 2 [cited 2017 Oct 17];8(4):192–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20811963.

  36. Bauer D, Krege J, Lane N, Leary E, Libanati C, Miller P, et al. National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges. Osteoporos Int [Internet]. 2012 Oct 14 [cited 2017 Oct 17];23(10):2425–33. Available from: http://link.springer.com/10.1007/s00198-012-2049-z

  37. Wang Y, Li L, Moore BT, Peng X-H, Fang X, Lappe JM, et al. MiR-133a in human circulating monocytes: a potential biomarker associated with postmenopausal osteoporosis. Huang Q, editor. PLoS One [Internet]. 2012 Apr 10 [cited 2017 Oct 17];7(4):e34641. Available from: http://dx.plos.org/10.1371/journal.pone.0034641

  38. Chen C, Cheng P, Xie H, Zhou H-D, Wu X-P, Liao E-Y, et al. MiR-503 regulates osteoclastogenesis via targeting RANK. J Bone Miner Res [Internet]. 2014 Feb [cited 2017 Oct 17];29(2):338–47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23821519.

  39. Li H, Wang Z, Fu Q, Zhang J. Plasma miRNA levels correlate with sensitivity to bone mineral density in postmenopausal osteoporosis patients. Biomarkers [Internet]. 2014 Nov 18 [cited 2017 Oct 17];19(7):553–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25231354.

  40. Ralston SH, Galwey N, MacKay I, Albagha OME, Cardon L, Compston JE, et al. Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: the FAMOS study. Hum Mol Genet [Internet]. 2005 Apr 1 [cited 2017 Oct 17];14(7):943–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15746152.

  41. Hsu Y-H, Zillikens MC, Wilson SG, Farber CR, Demissie S, Soranzo N, et al. An integration of genome-wide association study and gene expression profiling to prioritize the discovery of novel susceptibility loci for osteoporosis-related traits. Visscher PM, editor. PLoS Genet [Internet]. 2010 Jun 10 [cited 2017 Oct 17];6(6):e1000977. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20548944.

  42. • 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 [Internet]. 2014 Aug [cited 2017 Oct 17];29(8):1718–28. Available from: http://doi.wiley.com/10.1002/jbmr.2175. A study comparing miRNA signatures in serum and bone tissue.

  43. Panach L, Mifsut D, Tarín JJ, Cano A, García-Pérez MÁ. Serum circulating microRNAs as biomarkers of osteoporotic fracture. Calcif Tissue Int [Internet]. 2015 Nov 11 [cited 2017 Oct 17];97(5):495–505. Available from: http://link.springer.com/10.1007/s00223-015-0036-z

  44. Kocijan R, Muschitz C, Geiger E, Skalicky S, Baierl A, Dormann R, et al. Circulating microRNA signatures in patients with idiopathic and postmenopausal osteoporosis and fragility fractures. J Clin Endocrinol Metab [Internet]. 2016 Nov [cited 2017 Oct 14];101(11):4125–34. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27552543.

  45. • Heilmeier U, Hackl M, Skalicky S, Weilner S, Schroeder F, Vierlinger K, et al. Serum miRNA signatures are indicative of skeletal fractures in postmenopausal women with and without type 2 diabetes and influence osteogenic and adipogenic differentiation of adipose tissue-derived mesenchymal stem cells in vitro. J Bone Miner Res [Internet]. 2016 Dec [cited 2017 Oct 14];31(12):2173–92. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27345526. A comprehensive study identifying miRNA signatures that are indicative of skeletal fractures in diabetic bone disease and postmenopausal osteoprosis.

  46. Suomi S, Taipaleenmäki H, Seppänen A, Ripatti T, Väänänen K, Hentunen T, et al. MicroRNAs regulate osteogenesis and chondrogenesis of mouse bone marrow stromal cells. Gene Regul Syst Bio [Internet]. 2008 Apr 22 [cited 2017 Oct 17];2:177–91. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19787082.

  47. Sugatani T, Hruska KA. MicroRNA-223 is a key factor in osteoclast differentiation. J Cell Biochem [Internet]. 2007 Jul 1 [cited 2017 Oct 17];101(4):996–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17471500.

  48. •• Krzeszinski JY, Wei W, Huynh H, Jin Z, Wang X, Chang T-C, et al. miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature [Internet]. 2014 Aug 28 [cited 2017 Oct 17];512(7515):431–5. Available from: http://www.nature.com/doifinder/10.1038/nature13375. By using several genetic and pharmacological approached, this study demonstrates the important role of miR-34a in osteoporosis and bone metastasis.

  49. Zhang XH, Geng GL, Su B, Liang CP, Wang F, Bao JC. MicroRNA-338-3p inhibits glucocorticoid-induced osteoclast formation through RANKL targeting. Genet Mol Res [Internet]. 2016 Aug 26 [cited 2017 Oct 17];15(3). Available from: http://www.funpecrp.com.br/gmr/year2016/vol15-3/pdf/gmr7674.pdf.

  50. Shi C, Qi J, Huang P, Jiang M, Zhou Q, Zhou H, et al. MicroRNA-17/20a inhibits glucocorticoid-induced osteoclast differentiation and function through targeting RANKL expression in osteoblast cells. Bone [Internet]. 2014 Nov [cited 2017 Oct 17];68:67–75. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25138550.

  51. Bae Y, Yang T, Zeng H-C, Campeau PM, Chen Y, Bertin T, et al. miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet [Internet]. 2012 Jul 1 [cited 2017 Oct 17];21(13):2991–3000. Available from: https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/dds129.

  52. Wei J, Shi Y, Zheng L, Zhou B, Inose H, Wang J, et al. miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2. J Cell Biol [Internet]. 2012 May 14 [cited 2017 Oct 17];197(4):509–21. Available from: http://www.jcb.org/lookup/doi/10.1083/jcb.201201057.

  53. Chen L, HolmstrØm K, Qiu W, Ditzel N, Shi K, Hokland L, et al. MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells. Stem Cells [Internet]. 2014 Apr [cited 2017 Oct 17];32(4):902–12. Available from: http://doi.wiley.com/10.1002/stem.1615.

  54. Eskildsen T, Taipaleenmaki H, Stenvang J, Abdallah BM, Ditzel N, Nossent AY, et al. MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci [Internet]. 2011 Apr 12 [cited 2017 Oct 14];108(15):6139–44. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21444814.

  55. Li H, Xie H, Liu W, Hu R, Huang B, Tan Y-F, et al. A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest [Internet]. 2009 Dec 1 [cited 2017 Oct 17];119(12):3666–77. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19920351.

  56. Wang X, Guo B, Li Q, Peng J, Yang Z, Wang A, et al. miR-214 targets ATF4 to inhibit bone formation. Nat Med [Internet]. 2012 Dec 9 [cited 2017 Oct 14];19(1):93–100. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23223004.

  57. •• Li D, Liu J, Guo B, Liang C, Dang L, Lu C, et al. Osteoclast-derived exosomal miR-214-3p inhibits osteoblastic bone formation. Nat Commun [Internet]. 2016 Mar 7 [cited 2017 Oct 14];7:10872. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26947250. An exiting study demonstrating that secreted miRNAs can regulate cell-cell communication in bone.

  58. Zhao C, Sun W, Zhang P, Ling S, Li Y, Zhao D, et al. miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway. RNA Biol [Internet]. 2015 Mar 4 [cited 2017 Oct 14];12(3):343–53. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25826666.

  59. Wang F-S, Chuang P-C, Chung P-C, Lin C-L, Chen M-W, Ke H-J, et al. MicroRNA-29a protects against glucocorticoid-induced bone loss and fragility in rats by orchestrating bone acquisition and resorption. Arthritis Rheum [Internet]. 2013 Jun [cited 2017 Oct 17];65(6):1530–40. Available from: http://doi.wiley.com/10.1002/art.37948.

  60. Ko J-Y, Chuang P-C, Ke H-J, Chen Y-S, Sun Y-C, Wang F-S. MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation. Bone [Internet]. 2015 Dec [cited 2017 Oct 17];81:80–8. Available from: http://linkinghub.elsevier.com/retrieve/pii/S8756328215002598.

  61. Ko J-Y, Chuang P-C, Chen M-W, Ke H-C, Wu S-L, Chang Y-H, et al. MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast differentiation by regulating β-catenin acetylation. Bone [Internet]. 2013 Dec [cited 2017 Oct 17];57(2):468–75. Available from: http://linkinghub.elsevier.com/retrieve/pii/S8756328213003736.

  62. Cheng P, Chen C, He H-B, Hu R, Zhou H-D, Xie H, et al. miR-148a regulates osteoclastogenesis by targeting V-maf musculoaponeurotic fibrosarcoma oncogene homolog B. J Bone Miner Res [Internet]. 2013 May [cited 2017 Oct 17];28(5):1180–90. Available from: http://doi.wiley.com/10.1002/jbmr.1845

  63. Rokavec M, Li H, Jiang L, Hermeking H. The p53/miR-34 axis in development and disease. J Mol Cell Biol [Internet]. 2014 Jun 1 [cited 2017 Oct 17];6(3):214–30. Available from: http://www.ncbi.nlm.nih.gov/pubmed/24815299.

  64. van der Deen M, Taipaleenmäki H, Zhang Y, Teplyuk NM, Gupta A, Cinghu S, et al. MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma. J Biol Chem [Internet]. 2013 Jul 19 [cited 2016 Apr 28];288(29):21307–19. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3774399&tool=pmcentrez&rendertype=abstract.

  65. Cong F, Wu N, Tian X, Fan J, Liu J, Song T, et al. MicroRNA-34c promotes osteoclast differentiation through targeting LGR4. Gene [Internet]. 2017 Apr 30 [cited 2017 Oct 17];610:1–8. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0378111917300501.

  66. Janssen HLA, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, et al. Treatment of HCV infection by targeting microRNA. N Engl J Med [Internet]. 2013 May 2 [cited 2017 Oct 17];368(18):1685–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23534542.

  67. Liang C, Guo B, Wu H, Shao N, Li D, Liu J, et al. Aptamer-functionalized lipid nanoparticles targeting osteoblasts as a novel RNA interference-based bone anabolic strategy. Nat Med [Internet]. 2015 Mar 9 [cited 2017 Oct 17];21(3):288–94. Available from: http://www.nature.com/doifinder/10.1038/nm.3791.

  68. Wang X, Guo B, Li Q, Peng J, Yang Z, Wang A, et al. miR-214 targets ATF4 to inhibit bone formation. Nat Med [Internet]. 2012 Dec 9 [cited 2017 Oct 17];19(1):93–100. Available from: http://www.nature.com/doifinder/10.1038/nm.3026.

  69. Komori T. Glucocorticoid signaling and bone biology. Horm Metab Res [Internet]. 2016 Nov 21 [cited 2017 Oct 14];48(11):755–63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27871116.

  70. Wang F-S, Chung P-C, Lin C-L, Chen M-W, Ke H-J, Chang Y-H, et al. MicroRNA-29a protects against glucocorticoid-induced bone loss and fragility in rats by orchestrating bone acquisition and resorption. Arthritis Rheum [Internet]. 2013 Jun [cited 2017 Oct 14];65(6):1530–40. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23529662.

  71. Ko J-Y, Chuang P-C, Ke H-J, Chen Y-S, Sun Y-C, Wang F-S. MicroRNA-29a mitigates glucocorticoid induction of bone loss and fatty marrow by rescuing Runx2 acetylation. Bone [Internet]. 2015 Dec [cited 2017 Oct 14];81:80–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26141838.

  72. Liu P, Baumgart M, Groth M, Wittmann J, Jäck H-M, Platzer M, et al. Dicer ablation in osteoblasts by Runx2 driven cre-loxP recombination affects bone integrity, but not glucocorticoid-induced suppression of bone formation. Sci Rep [Internet]. 2016 Aug 24 [cited 2017 Oct 17];6(1):32112. Available from: http://www.nature.com/articles/srep32112.

  73. Kapinas K, Kessler C, Ricks T, Gronowicz G, Delany AM. miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem [Internet]. 2010 Aug 13 [cited 2017 Oct 17];285(33):25221–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20551325.

  74. Kong X, Yu J, Bi J, Qi H, Di W, Wu L, et al. Glucocorticoids transcriptionally regulate miR-27b expression promoting body fat accumulation via suppressing the browning of white adipose tissue. Diabetes [Internet]. 2015 Feb [cited 2017 Oct 17];64(2):393–404. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25187367.

  75. • Dole NS, Delany AM. MicroRNA variants as genetic determinants of bone mass. Bone [Internet]. 2016 Mar [cited 2017 Oct 17];84:57–68. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26723575. A recent review discussing the role of miRNA variant as genetic determinants of bone mass.

  76. Lei S-F, Papasian CJ, Deng H-W. Polymorphisms in predicted miRNA binding sites and osteoporosis. J Bone Miner Res [Internet]. 2011 Jan [cited 2017 Oct 17];26(1):72–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20641033.

  77. Delany AM, McMahon DJ, Powell JS, Greenberg DA, Kurland ES. Osteonectin/SPARC polymorphisms in Caucasian men with idiopathic osteoporosis. Osteoporos Int [Internet]. 2008 Jul 15 [cited 2017 Oct 17];19(7):969–78. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18084690.

  78. Dole NS, Kapinas K, Kessler CB, Yee S-P, Adams DJ, Pereira RC, et al. A single nucleotide polymorphism in osteonectin 3′ untranslated region regulates bone volume and is targeted by miR-433. J Bone Miner Res [Internet]. 2015 Apr [cited 2017 Oct 17];30(4):723–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25262637.

  79. Wang Z, Lu Y, Zhang X, Ren X, Wang Y, Li Z, et al. Serum microRNA is a promising biomarker for osteogenesis imperfect. Intractable Rare Dis Res [Internet]. 2012 May [cited 2017 Oct 17];1(2):81–5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25343076.

  80. Ou M, Zhang X, Dai Y, Gao J, Zhu M, Yang X, et al. Identification of potential microRNA-target pairs associated with osteopetrosis by deep sequencing, iTRAQ proteomics and bioinformatics. Eur J Hum Genet [Internet]. 2014 May 2 [cited 2017 Oct 17];22(5):625–32. Available from: http://www.nature.com/doifinder/10.1038/ejhg.2013.221

  81. Browne G, Taipaleenmäki H, Stein GS, Stein JL, Lian JB. MicroRNAs in the control of metastatic bone disease. Trends Endocrinol Metab [Internet]. 2014 Jun [cited 2016 Apr 28];25(6):320–7. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=4075094&tool=pmcentrez&rendertype=abstract.

  82. Taipaleenmäki H, Farina NH, van Wijnen AJ, Stein JL, Hesse E, Stein GS, et al. Antagonizing miR-218-5p attenuates Wnt signaling and reduces metastatic bone disease of triple negative breast cancer cells. Oncotarget [Internet]. 2016 Oct 12 [cited 2017 Oct 17];7(48):79032–46. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27738322.

Download references

Author information

Authors and Affiliations

  1. Molecular Skeletal Biology Laboratory, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Research Campus N27, Martinistrasse 52, 20246, Hamburg, Germany

    Hanna Taipaleenmäki

Authors
  1. Hanna Taipaleenmäki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hanna Taipaleenmäki.

Ethics declarations

Conflict of Interest

Hannah Taipaleenmäki declares no conflict 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.

Additional information

This article is part of the Topical Collection on Genetics

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taipaleenmäki, H. Regulation of Bone Metabolism by microRNAs. Curr Osteoporos Rep 16, 1–12 (2018). https://doi.org/10.1007/s11914-018-0417-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-018-0417-0

Keywords

Search

Navigation