Advertisement

Current Molecular Biology Reports

, Volume 5, Issue 1, pp 55–64 | Cite as

MICROmanagement of Runx2 Function in Skeletal Cells

  • Benjamin J. Wildman
  • Tanner C. Godfrey
  • Mohammad Rehan
  • Yuechuan Chen
  • Lubana H. Afreen
  • Quamarul HassanEmail author
MicroRNAs in Skeletal Development (A Delany, Section Editor)
  • 9 Downloads
Part of the following topical collections:
  1. Topical Collection on MicroRNAs in Skeletal Development

Abstract

Purpose of Review

Precise and temporal expression of Runx2 and its regulatory transcriptional network is a key determinant for the intricate cellular and developmental processes in adult bone tissue formation. This review analyzes how microRNA functions to regulate this network, and how dysregulation results in bone disorders.

Recent Findings

Similar to other biologic processes, microRNA (miRNA/miR) regulation is undeniably indispensable to bone synthesis and maintenance. There exists a miRNA–RUNX2 network where RUNX2 regulates the transcription of miRs or is post-transcriptionally regulated by a class of miRs, forming a variety of miR-RUNX2 regulatory pathways which regulate osteogenesis.

Summary

The current review provides insights to understand transcriptional–post-transcriptional regulatory network governed by Runx2 and osteogenic miRs, and is based largely from in vitro and in vivo studies. When taken together, this article discusses a new regulatory layer of bone tissue-specific gene expression by RUNX2 influenced via miRNA.

Keywords

MicroRNA Runx2 Osteoblast differentiation Post-transcriptional repression Noncoding RNA Osteoblastogenesis 

Notes

Acknowledgments

We thank the members of RNA Biology and Epigenetics laboratory, School of Dentistry, UAB, for assistance with critical comments, valuable suggestions, and support. We are thankful to the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIH/NIAMS) under Award Number 1R01AR069578 supported research for this publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information

We are thankful to the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIH/NIAMS) under Award Number 1R01AR069578 supported research for this publication.

Compliance with Ethical Standards

Conflict of Interest

Benjamin J. Wildman, Tanner C. Godfrey, Mohammad Rehan, Yuechuan Chen, Lubana H. Afreen, and Quamarul Hassan each declare that they have no conflicts of interest with the contents of this article.

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.

References

  1. 1.
    Vaquerizas JM, Kummerfeld SK, Teichmann SA, Luscombe NM. A census of human transcription factors: function, expression and evolution. Nat Rev Genet. 2009;10(4):252–63.  https://doi.org/10.1038/nrg2538.CrossRefPubMedGoogle Scholar
  2. 2.
    Komori T. Regulation of osteoblast differentiation by Runx2. Adv Exp Med Biol. 2010;658:43–9.  https://doi.org/10.1007/978-1-4419-1050-9_5.CrossRefPubMedGoogle Scholar
  3. 3.
    Iyer MK, Niknafs YS, Malik R, Singhal U, Sahu A, Hosono Y, et al. The landscape of long noncoding RNAs in the human transcriptome. Nat Genet. 2015;47(3):199–208.  https://doi.org/10.1038/ng.3192.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. 2004;10(12):1957–66.  https://doi.org/10.1261/rna.7135204.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Hassan MQ, Tye CE, Stein GS, Lian JB. Non-coding RNAs: epigenetic regulators of bone development and homeostasis. Bone. 2015;81:746–56.  https://doi.org/10.1016/j.bone.2015.05.026.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425(6956):415–9.  https://doi.org/10.1038/nature01957.CrossRefPubMedGoogle Scholar
  7. 7.
    Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21(17):4663–70.CrossRefGoogle Scholar
  8. 8.
    Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051–60.  https://doi.org/10.1038/sj.emboj.7600385.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18(24):3016–27.  https://doi.org/10.1101/gad.1262504.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wang X, Xu X, Ma Z, Huo Y, Xiao Z, Li Y, et al. Dynamic mechanisms for pre-miRNA binding and export by Exportin-5. RNA. 2011;17(8):1511–28.  https://doi.org/10.1261/rna.2732611.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Song MS, Rossi JJ. Molecular mechanisms of dicer: endonuclease and enzymatic activity. Biochem J. 2017;474(10):1603–18.  https://doi.org/10.1042/BCJ20160759.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Pratt AJ, MacRae IJ. The RNA-induced silencing complex: a versatile gene-silencing machine. J Biol Chem. 2009;284(27):17897–901.  https://doi.org/10.1074/jbc.R900012200.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Wang B, Li S, Qi HH, Chowdhury D, Shi Y, Novina CD. Distinct passenger strand and mRNA cleavage activities of human Argonaute proteins. Nat Struct Mol Biol. 2009;16(12):1259–66.  https://doi.org/10.1038/nsmb.1712.CrossRefPubMedGoogle Scholar
  14. 14.
    Hu R, Liu W, Li H, Yang L, Chen C, Xia ZY, et al. A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation. J Biol Chem. 2011;286(14):12328–39.  https://doi.org/10.1074/jbc.M110.176099.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Huang J, Zhao L, Xing L, Chen D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2010;28(2):357–64.  https://doi.org/10.1002/stem.288.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Li Z, Hassan MQ, Volinia S, van Wijnen AJ, Stein JL, Croce CM, et al. A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci U S A. 2008;105(37):13906–11.  https://doi.org/10.1073/pnas.0804438105.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Wu T, Zhou H, Hong Y, Li J, Jiang X, Huang H. miR-30 family members negatively regulate osteoblast differentiation. J Biol Chem. 2012;287(10):7503–11.  https://doi.org/10.1074/jbc.M111.292722.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ge J, Guo S, Fu Y, Zhou P, Zhang P, Du Y, et al. Dental follicle cells participate in tooth eruption via the RUNX2-MiR-31-SATB2 loop. J Dent Res. 2015;94(7):936–44.  https://doi.org/10.1177/0022034515578908.CrossRefPubMedGoogle Scholar
  19. 19.
    Hassan MQ, Gordon JA, Beloti MM, Croce CM, van Wijnen AJ, 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 U S A. 2010;107(46):19879–84.  https://doi.org/10.1073/pnas.1007698107.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Heair HM, Kemper AG, Roy B, Lopes HB, Rashid H, Clarke JC, et al. MicroRNA 665 regulates dentinogenesis through MicroRNA-mediated silencing and epigenetic mechanisms. Mol Cell Biol. 2015;35(18):3116–30.  https://doi.org/10.1128/MCB.00093-15.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kang IH, Jeong BC, Hur SW, Choi H, Choi SH, Ryu JH, et al. MicroRNA-302a stimulates osteoblastic differentiation by repressing COUP-TFII expression. J Cell Physiol. 2015;230(4):911–21.  https://doi.org/10.1002/jcp.24822.CrossRefPubMedGoogle Scholar
  22. 22.
    Yu S, Geng Q, Pan Q, Liu Z, Ding S, Xiang Q, et al. MiR-690, a Runx2-targeted miRNA, regulates osteogenic differentiation of C2C12 myogenic progenitor cells by targeting NF-kappaB p65. Cell Biosci. 2016;6:10.  https://doi.org/10.1186/s13578-016-0073-y.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    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. 2012;8(4):212–27.  https://doi.org/10.1038/nrendo.2011.234.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ, et al. A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci U S A. 2011;108(24):9863–8.  https://doi.org/10.1073/pnas.1018493108.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Xu C, Zhang H, Gu W, Wu H, Chen Y, Zhou W, et al. The microRNA-10a/ID3/RUNX2 axis modulates the development of ossification of posterior longitudinal ligament. Sci Rep. 2018;8(1):9225.  https://doi.org/10.1038/s41598-018-27514-x.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Papaioannou G, Mirzamohammadi F, Kobayashi T. MicroRNAs involved in bone formation. Cell Mol Life Sci. 2014;71(24):4747–61.  https://doi.org/10.1007/s00018-014-1700-6.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Vimalraj S, Partridge NC, Selvamurugan N. A positive role of microRNA-15b on regulation of osteoblast differentiation. J Cell Physiol. 2014;229(9):1236–44.  https://doi.org/10.1002/jcp.24557.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, et al. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem. 2009;284(23):15676–84.  https://doi.org/10.1074/jbc.M809787200.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Mizoguchi F, Murakami Y, Saito T, Miyasaka N, Kohsaka H. miR-31 controls osteoclast formation and bone resorption by targeting RhoA. Arthritis Res Ther. 2013;15(5):R102.  https://doi.org/10.1186/ar4282.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Xie Q, Wang Z, Bi X, Zhou H, Wang Y, Gu P, et al. Effects of miR-31 on the osteogenesis of human mesenchymal stem cells. Biochem Biophys Res Commun. 2014;446(1):98–104.  https://doi.org/10.1016/j.bbrc.2014.02.058.CrossRefPubMedGoogle Scholar
  31. 31.
    Deng Y, Wu S, Zhou H, Bi X, Wang Y, Hu Y, et al. Effects of a miR-31, Runx2, and Satb2 regulatory loop on the osteogenic differentiation of bone mesenchymal stem cells. Stem Cells Dev. 2013;22(16):2278–86.  https://doi.org/10.1089/scd.2012.0686.CrossRefPubMedGoogle Scholar
  32. 32.
    Stepicheva NA, Song JL. Function and regulation of microRNA-31 in development and disease. Mol Reprod Dev. 2016;83(8):654–74.  https://doi.org/10.1002/mrd.22678.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Bae Y, Yang T, Zeng HC, Campeau PM, Chen Y, Bertin T, et al. miRNA-34c regulates notch signaling during bone development. Hum Mol Genet. 2012;21(13):2991–3000.  https://doi.org/10.1093/hmg/dds129.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Engin F, Yao Z, Yang T, Zhou G, Bertin T, Jiang MM, et al. Dimorphic effects of notch signaling in bone homeostasis. Nat Med. 2008;14(3):299–305.  https://doi.org/10.1038/nm1712.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Zuo B, Zhu J, Li J, Wang C, Zhao X, Cai G, et al. microRNA-103a functions as a mechanosensitive microRNA to inhibit bone formation through targeting Runx2. J Bone Miner Res. 2015;30(2):330–45.  https://doi.org/10.1002/jbmr.2352.CrossRefPubMedGoogle Scholar
  36. 36.
    Cheung KS, Sposito N, Stumpf PS, Wilson DI, Sanchez-Elsner T, Oreffo RO. MicroRNA-146a regulates human foetal femur derived skeletal stem cell differentiation by down-regulating SMAD2 and SMAD3. PLoS One. 2014;9(6):e98063.  https://doi.org/10.1371/journal.pone.0098063.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Tu B, Liu S, Yu B, Zhu J, Ruan H, Tang T, et al. miR-203 inhibits the traumatic heterotopic ossification by targeting Runx2. Cell Death Dis. 2016;7(10):e2436.  https://doi.org/10.1038/cddis.2016.325.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Zhang Y, Gao Y, Cai L, Li F, Lou Y, Xu N, et al. MicroRNA-221 is involved in the regulation of osteoporosis through regulates RUNX2 protein expression and osteoblast differentiation. Am J Transl Res. 2017;9(1):126–35.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Hamam D, Ali D, Vishnubalaji R, Hamam R, Al-Nbaheen M, Chen L, et al. microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells. Cell Death Dis. 2014;5:e1499.  https://doi.org/10.1038/cddis.2014.462.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Zhao W, Zhang S, Wang B, Huang J, Lu WW, Chen D. Runx2 and microRNA regulation in bone and cartilage diseases. Ann N Y Acad Sci. 2016;1383(1):80–7.  https://doi.org/10.1111/nyas.13206.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Gamez B, Rodriguez-Carballo E, Bartrons R, Rosa JL, Ventura F. MicroRNA-322 (miR-322) and its target protein Tob2 modulate Osterix (Osx) mRNA stability. J Biol Chem. 2013;288(20):14264–75.  https://doi.org/10.1074/jbc.M112.432104.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Itoh T, Ando M, Tsukamasa Y, Akao Y. Expression of BMP-2 and Ets1 in BMP-2-stimulated mouse pre-osteoblast differentiation is regulated by microRNA-370. FEBS Lett. 2012;586(12):1693–701.  https://doi.org/10.1016/j.febslet.2012.04.014.CrossRefPubMedGoogle Scholar
  43. 43.
    Zhang Z, Hou C, Meng F, Zhao X, Huang G, Chen W, et al. MiR-455-3p regulates early chondrogenic differentiation via inhibiting Runx2. FEBS Lett. 2015;589(23):3671–8.  https://doi.org/10.1016/j.febslet.2015.09.032.CrossRefPubMedGoogle Scholar
  44. 44.
    Kureel J, John AA, Dixit M, Singh D. MicroRNA-467g inhibits new bone regeneration by targeting Ihh/Runx-2 signaling. Int J Biochem Cell Biol. 2017;85:35–43.  https://doi.org/10.1016/j.biocel.2017.01.018.CrossRefPubMedGoogle Scholar
  45. 45.
    Chen H, Ji X, She F, Gao Y, Tang P. miR-628-3p regulates osteoblast differentiation by targeting RUNX2: possible role in atrophic non-union. Int J Mol Med. 2017;39(2):279–86.  https://doi.org/10.3892/ijmm.2016.2839.CrossRefPubMedGoogle Scholar
  46. 46.
    Liao L, Yang X, Su X, Hu C, Zhu X, Yang N, et al. Redundant miR-3077-5p and miR-705 mediate the shift of mesenchymal stem cell lineage commitment to adipocyte in osteoporosis bone marrow. Cell Death Dis. 2013;4:e600.  https://doi.org/10.1038/cddis.2013.130.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Li H, Xie H, Liu W, Hu R, Huang B, Tan YF, et al. A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest. 2009;119(12):3666–77.  https://doi.org/10.1172/JCI39832.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Liu H, Zhong L, Yuan T, Chen S, Zhou Y, An L, et al. MicroRNA-155 inhibits the osteogenic differentiation of mesenchymal stem cells induced by BMP9 via downregulation of BMP signaling pathway. Int J Mol Med. 2018;41(6):3379–93.  https://doi.org/10.3892/ijmm.2018.3526.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Tome M, Lopez-Romero P, Albo C, Sepulveda JC, Fernandez-Gutierrez B, Dopazo A, et al. miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ. 2011;18(6):985–95.  https://doi.org/10.1038/cdd.2010.167.CrossRefPubMedGoogle Scholar
  50. 50.
    Zhang J, Tu Q, Bonewald LF, He X, Stein G, Lian J, et al. Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1. J Bone Miner Res. 2011;26(8):1953–63.  https://doi.org/10.1002/jbmr.377.CrossRefPubMedGoogle Scholar
  51. 51.
    Zhang L, Tang Y, Zhu X, Tu T, Sui L, Han Q, et al. Overexpression of MiR-335-5p promotes bone formation and regeneration in mice. J Bone Miner Res. 2017;32(12):2466–75.  https://doi.org/10.1002/jbmr.3230.CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Grunhagen J, Bhushan R, Degenkolbe E, Jager M, Knaus P, Mundlos S, et al. MiR-497 approximately 195 cluster microRNAs regulate osteoblast differentiation by targeting BMP signaling. J Bone Miner Res. 2015;30(5):796–808.  https://doi.org/10.1002/jbmr.2412.CrossRefPubMedGoogle Scholar
  53. 53.
    Almeida MI, Silva AM, Vasconcelos DM, Almeida CR, Caires H, Pinto MT, et al. miR-195 in human primary mesenchymal stromal/stem cells regulates proliferation, osteogenesis and paracrine effect on angiogenesis. Oncotarget. 2016;7(1):7–22.  https://doi.org/10.18632/oncotarget.6589.CrossRefPubMedGoogle Scholar
  54. 54.
    Wang Y, Chen S, Deng C, Li F, Wang Y, Hu X, et al. MicroRNA-204 targets Runx2 to attenuate BMP-2-induced osteoblast differentiation of human aortic valve interstitial cells. J Cardiovasc Pharmacol. 2015;66(1):63–71.  https://doi.org/10.1097/FJC.0000000000000244.CrossRefPubMedGoogle Scholar
  55. 55.
    Cui RR, Li SJ, Liu LJ, Yi L, Liang QH, Zhu X, et al. MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo. Cardiovasc Res. 2012;96(2):320–9.  https://doi.org/10.1093/cvr/cvs258.CrossRefPubMedGoogle Scholar
  56. 56.
    Yu C, Li L, Xie F, Guo S, Liu F, Dong N, et al. LncRNA TUG1 sponges miR-204-5p to promote osteoblast differentiation through upregulating Runx2 in aortic valve calcification. Cardiovasc Res. 2018;114(1):168–79.  https://doi.org/10.1093/cvr/cvx180.CrossRefPubMedGoogle Scholar
  57. 57.
    Zhang Y, Xie RL, Gordon J, LeBlanc K, Stein JL, Lian JB, et al. Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. J Biol Chem. 2012;287(26):21926–35.  https://doi.org/10.1074/jbc.M112.340398.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Fakhry M, Hamade E, Badran B, Buchet R, Magne D. Molecular mechanisms of mesenchymal stem cell differentiation towards osteoblasts. World J Stem Cells. 2013;5(4):136–48.  https://doi.org/10.4252/wjsc.v5.i4.136.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Sun Q, Liu H, Lin H, Yuan G, Zhang L, Chen Z. MicroRNA-338-3p promotes differentiation of mDPC6T into odontoblast-like cells by targeting Runx2. Mol Cell Biochem. 2013;377(1–2):143–9.  https://doi.org/10.1007/s11010-013-1580-3.CrossRefPubMedGoogle Scholar
  60. 60.
    Liu H, Sun Q, Wan C, Li L, Zhang L, Chen Z. MicroRNA-338-3p regulates osteogenic differentiation of mouse bone marrow stromal stem cells by targeting Runx2 and Fgfr2. J Cell Physiol. 2014;229(10):1494–502.  https://doi.org/10.1002/jcp.24591.CrossRefPubMedGoogle Scholar
  61. 61.
    Zaragosi LE, Wdziekonski B, Brigand KL, Villageois P, Mari B, Waldmann R, et al. Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis. Genome Biol. 2011;12(7):R64.  https://doi.org/10.1186/gb-2011-12-7-r64.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Zhang R, Yan S, Wang J, Deng F, Guo Y, Li Y, et al. MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2. Tumour Biol. 2016;37(3):3479–88.  https://doi.org/10.1007/s13277-015-4086-7.CrossRefPubMedGoogle Scholar
  63. 63.
    Balderman JA, Lee HY, Mahoney CE, Handy DE, White K, Annis S, et al. Bone morphogenetic protein-2 decreases microRNA-30b and microRNA-30c to promote vascular smooth muscle cell calcification. J Am Heart Assoc. 2012;1(6):e003905.  https://doi.org/10.1161/JAHA.112.003905.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Gay I, Cavender A, Peto D, Sun Z, Speer A, Cao H, et al. Differentiation of human dental stem cells reveals a role for microRNA-218. J Periodontal Res. 2014;49(1):110–20.  https://doi.org/10.1111/jre.12086.CrossRefPubMedGoogle Scholar
  65. 65.
    Yan J, Guo D, Yang S, Sun H, Wu B, Zhou D. Inhibition of miR-222-3p activity promoted osteogenic differentiation of hBMSCs by regulating Smad5-RUNX2 signal axis. Biochem Biophys Res Commun. 2016;470(3):498–503.  https://doi.org/10.1016/j.bbrc.2016.01.133.CrossRefPubMedGoogle Scholar
  66. 66.
    Yeh CH, Jin L, Shen F, Balian G, Li XJ. miR-221 attenuates the osteogenic differentiation of human annulus fibrosus cells. Spine J. 2016;16(7):896–904.  https://doi.org/10.1016/j.spinee.2016.03.026.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Kim DS, Lee SY, Lee JH, Bae YC, Jung JS. MicroRNA-103a-3p controls proliferation and osteogenic differentiation of human adipose tissue-derived stromal cells. Exp Mol Med. 2015;47:e172.  https://doi.org/10.1038/emm.2015.39.CrossRefPubMedGoogle Scholar
  68. 68.
    van der Deen M, Taipaleenmaki 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. 2013;288(29):21307–19.  https://doi.org/10.1074/jbc.M112.445890.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Saini S, Majid S, Yamamura S, Tabatabai L, Suh SO, Shahryari V, et al. Regulatory role of mir-203 in prostate cancer progression and metastasis. Clin Cancer Res. 2011;17(16):5287–98.  https://doi.org/10.1158/1078-0432.CCR-10-2619.CrossRefPubMedGoogle Scholar
  70. 70.
    Pratap J, Lian JB, Javed A, Barnes GL, van Wijnen AJ, Stein JL, et al. Regulatory roles of Runx2 in metastatic tumor and cancer cell interactions with bone. Cancer Metastasis Rev. 2006;25(4):589–600.  https://doi.org/10.1007/s10555-006-9032-0.CrossRefPubMedGoogle Scholar
  71. 71.
    Taipaleenmaki H, Browne G, Akech J, Zustin J, van Wijnen AJ, Stein JL, et al. Targeting of Runx2 by miR-135 and miR-203 impairs progression of breast cancer and metastatic bone disease. Cancer Res. 2015;75(7):1433–44.  https://doi.org/10.1158/0008-5472.CAN-14-1026.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Chang WM, Lin YF, Su CY, Peng HY, Chang YC, Lai TC, et al. Dysregulation of RUNX2/Activin-A Axis upon miR-376c downregulation promotes lymph node metastasis in head and neck squamous cell carcinoma. Cancer Res. 2016;76(24):7140–50.  https://doi.org/10.1158/0008-5472.CAN-16-1188.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Benjamin J. Wildman
    • 1
  • Tanner C. Godfrey
    • 1
  • Mohammad Rehan
    • 1
  • Yuechuan Chen
    • 1
  • Lubana H. Afreen
    • 1
  • Quamarul Hassan
    • 1
    • 2
    Email author
  1. 1.RNA Biology and Epigenetics Laboratory, Department of Oral and Maxillofacial Surgery, School of DentistryUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Oral and Maxillofacial Surgery, School of DentistryUniversity of Alabama at BirminghamBirminghamUSA

Personalised recommendations