Cell and Tissue Research

, Volume 368, Issue 2, pp 229–238 | Cite as

MicroRNAs in regulation of osteogenic differentiation of mesenchymal stem cells



Mesenchymal stem cells (MSCs), also referred to as multipotent stromal cells, have been isolated from various adult tissue sources because of their capabilities of differentiating into multiple cell lineages including osteoblasts, thus providing a novel approach for treating bone diseases and metabolic disorders. Despite extensive potential in cell therapy and widespread interest in clinical applications of MSCs, the molecular mechanisms with regard to the regulation of their therapeutic properties and osteoblast differentiation remain to be fully elucidated. MicroRNAs (miRNAs), a novel class of endogenous small noncoding RNAs, regulate gene expressions by translational repression or degradation of their targets. Recently, emerging evidence has shown that miRNAs are closely involved in controlling the key steps of osteoblast differentiation in MSCs. This review focuses on miRNAs and their roles in regulating osteogenic differentiation of MSCs.


Mesenchymal stem cells microRNAs Osteogenesis Transcription factors Signaling pathways 



Mesenchymal stem cells



RNA pol II

RNA polymerase II


Primary miRNAs


Precursor miRNAs


RNA-induced silencing complex


3'Untranslated region


Human adipose tissue-derived mesenchymal stem cells


Alkaline phosphatase




Distal-less homeobox 5


Bone morphogenetic protein-2


Chromatin immunoprecipitation


Bone morphogenetic protein receptor type II


Histone deacetylase


Peroxisome proliferator-activated receptor-γ




Chicken ovalbumin upstream promoter-transcription factor II


Glycogen synthase kinase 3


Human umbilical cord mesenchymal stem cells


Secreted frizzled related protein 2


Erythroblastosis virus E26 oncogene homolog 1


Transforming growth factor-β


Authors’ contributions

CH and SW-J participated in the design of the review. CH contributed in table designing and review writing. JN-G searched for literature and helped to design figures. All authors read and approved the final manuscript.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.


  1. Akune T, Ohba S, Kamekura S, Yamaguchi M, Chung UI, Kubota N, Terauchi Y, Harada Y, Azuma Y, Nakamura K, Kadowaki T, Kawaguchi H (2004) PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 113:846–855CrossRefPubMedPubMedCentralGoogle Scholar
  2. Alliston T, Choy L, Ducy P, Karsenty G, Derynck R (2001) TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO J 20:2254–2272CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ba K, Yang X, Wu L, Wei X, Fu N, Fu Y, Cai X, Yao Y, Ge Y, Lin Y (2012) Jagged-1-mediated activation of notch signalling induces adipogenesis of adipose-derived stem cells. Cell Prolif 45:538–544CrossRefPubMedGoogle Scholar
  4. Bae Y, Yang T, Zeng HC, Campeau PM, Chen Y, Bertin T, Dawson BC, Munivez E, Tao J, Lee BH (2012) miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet 21:2991–3000CrossRefPubMedPubMedCentralGoogle Scholar
  5. Baglio SR, Devescovi V, Granchi D, Baldini N (2013) MicroRNA expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation reveals Osterix regulation by miR-31. Gene 527:321–331CrossRefPubMedGoogle Scholar
  6. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefPubMedGoogle Scholar
  7. Bhushan R, Grunhagen J, Becker J, Robinson PN, Ott CE, Knaus P (2012) miR-181a promotes osteoblastic differentiation through repression of TGF-beta signaling molecules. Int J Biochem Cell Biol 45:696–705CrossRefPubMedGoogle Scholar
  8. Boland GM, Perkins G, Hall DJ, Tuan RS (2004) Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem 93:1210–1230CrossRefPubMedGoogle Scholar
  9. Chen L, Holmstrom K, Qiu W, Ditzel N, Shi K, Hokland L, Kassem M (2014) MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells. Stem Cells 32:902–912CrossRefPubMedGoogle Scholar
  10. Chu Q, Liu L, Wang W (2013) Overexpression of hCLP46 enhances Notch activation and regulates cell proliferation in a cell type-dependent manner. Cell Prolif 46:254–262CrossRefPubMedGoogle Scholar
  11. Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8:739–750CrossRefPubMedGoogle Scholar
  12. De Boer J, Wang HJ, Van Blitterswijk C (2004a) Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng 10:393–401CrossRefPubMedGoogle Scholar
  13. De Boer J, Siddappa R, Gaspar C, van Apeldoorn A, Fodde R, van Blitterswijk C (2004b) Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells. Bone 34:818–826CrossRefPubMedGoogle Scholar
  14. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754CrossRefPubMedGoogle Scholar
  15. Erices A, Conget P, Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109:235–242CrossRefPubMedGoogle Scholar
  16. Etheridge SL, Spencer GJ, Heath DJ, Genever PG (2004) Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells. Stem Cells 22:849–860CrossRefPubMedGoogle Scholar
  17. Fang S, Deng Y, Gu P, Fan X (2015) MicroRNAs regulate bone development and regeneration. Int J Mol Sci 16:8227–8253CrossRefPubMedPubMedCentralGoogle Scholar
  18. Franceschi RT, Ge C, Xiao G, Roca H, Jiang D (2009) Transcriptional regulation of osteoblasts. Cells Tissues Organs 189:144–152CrossRefPubMedGoogle Scholar
  19. Gambardella A, Nagaraju CK, O’Shea PJ, Mohanty ST, Kottam L, Pilling J, Sullivan M, Djerbi M, Koopmann W, Croucher PI, Bellantuono I (2011) Glycogen synthase kinase-3alpha/beta inhibition promotes in vivo amplification of endogenous mesenchymal progenitors with osteogenic and adipogenic potential and their differentiation to the osteogenic lineage. J Bone Miner Res 26:811–821CrossRefPubMedGoogle Scholar
  20. Hamam D, Ali D, Vishnubalaji R, Hamam R, Al-Nbaheen M, Chen L, Kassem M, Aldahmash A, Alajez NM (2014) microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells. Cell Death Dis 5:e1499CrossRefPubMedPubMedCentralGoogle Scholar
  21. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531CrossRefPubMedGoogle Scholar
  22. Hu H, Zhang Y, Cai XH, Huang JF, Cai L (2012) Changes in microRNA expression in the MG-63 osteosarcoma cell line compared with osteoblasts. Oncol Lett 4:1037–1042PubMedPubMedCentralGoogle Scholar
  23. Hu R, Liu W, Li H, Yang L, Chen C, Xia ZY, Guo LJ, Xie H, Zhou HD, Wu XP, Luo XH (2011) A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation. J Biol Chem 286:12328–12339CrossRefPubMedPubMedCentralGoogle Scholar
  24. Huang J, Zhao L, Xing L, Chen D (2010) MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28:357–364PubMedPubMedCentralGoogle Scholar
  25. Huang S, Wang S, Bian C, Yang Z, Zhou H, Zeng Y, Li H, Han Q, Zhao RC (2012) Upregulation of miR-22 promotes osteogenic differentiation and inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells by repressing HDAC6 protein expression. Stem Cells Dev 21:2531–2540CrossRefPubMedPubMedCentralGoogle Scholar
  26. Huang W, Yang S, Shao J, Li YP (2007) Signaling and transcriptional regulation in osteoblast commitment and differentiation. Front Biosci 12:3068–3092CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hupkes M, van Someren EP, Middelkamp SH, Piek E, van Zoelen EJ, Dechering KJ (2011) DNA methylation restricts spontaneous multi-lineage differentiation of mesenchymal progenitor cells, but is stable during growth factor-induced terminal differentiation. Biochim Biophys Acta 1813:839–849CrossRefPubMedGoogle Scholar
  28. Hupkes M, Sotoca AM, Hendriks JM, van Zoelen EJ, Dechering KJ (2014) MicroRNA miR-378 promotes BMP2-induced osteogenic differentiation of mesenchymal progenitor cells. BMC Mol Biol 15:1CrossRefPubMedPubMedCentralGoogle Scholar
  29. Hwang S, Park SK, Lee HY, Kim SW, Lee JS, Choi EK, You D, Kim CS, Suh N (2014) miR-140-5p suppresses BMP2-mediated osteogenesis in undifferentiated human mesenchymal stem cells. FEBS Lett 588:2957–2963CrossRefPubMedGoogle Scholar
  30. Inose H, Ochi H, Kimura A, Fujita K, Xu R, Sato S, Iwasaki M, Sunamura S, Takeuchi Y, Mizuno Y, Yagi K, Tokuzawa Y, Kanesaki-Yatsuka Y, Suda T, Katagiri T, Fukuda T, Maruyama M, Okuda A, Amemiya T, Kondoh Y, Tashiro H, Okazaki Y (2008) miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation. Biochem Biophys Res Commun 368:267–272CrossRefGoogle Scholar
  31. Itoh T, Nozawa Y, Akao Y (2009) MicroRNA-141 and -200a are involved in bone morphogenetic protein-2-induced mouse pre-osteoblast differentiation by targeting distal-less homeobox 5. J Biol Chem 284:19272–19279CrossRefPubMedPubMedCentralGoogle Scholar
  32. Itoh T, Ando M, Tsukamasa Y, Akao Y (2012) Expression of BMP-2 and Ets1 in BMP-2-stimulated mouse pre-osteoblast differentiation is regulated by microRNA-370. FEBS Lett 586:1693–1701CrossRefPubMedGoogle Scholar
  33. Jeong BC, Kang IH, Hwang YC, Kim SH, Koh JT (2014) MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression. Cell Death Dis 5:e1532CrossRefPubMedPubMedCentralGoogle Scholar
  34. Jia J, Tian Q, Ling S, Liu Y, Yang S, Shao Z (2013) miR-145 suppresses osteogenic differentiation by targeting Sp7. FEBS Lett 587:3027–3031CrossRefPubMedGoogle Scholar
  35. Jia J, Feng X, Xu W, Yang S, Zhang Q, Liu X, Feng Y, Dai Z (2014) MiR-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis. Exp Mol Med 46:e107CrossRefPubMedPubMedCentralGoogle Scholar
  36. Kang IH, Jeong BC, Hur SW, Choi H, Choi SH, Ryu JH, Hwang YC, Koh JT (2014) MicroRNA-302a stimulates osteoblastic differentiation by repressing COUP-TFII expression. J Cell Physiol 230:911–921CrossRefGoogle Scholar
  37. Kapinas K, Kessler C, Ricks T, Gronowicz G, Delany AM (2010) miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem 285:25221–25231CrossRefPubMedPubMedCentralGoogle Scholar
  38. Katagiri T, Yamaguchi A, Komaki M, Abe E, Takahashi N, Ikeda T, Rosen V, Wozney JM, Fujisawa-Sehara A, Suda T (1994) Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. J Cell Biol 127:1755–1766CrossRefPubMedGoogle Scholar
  39. Kim EJ, Kang IH, Lee JW, Jang WG, Koh JT (2013) MiR-433 mediates ERRgamma-suppressed osteoblast differentiation via direct targeting to Runx2 mRNA in C3H10T1/2 cells. Life Sci 92:562–568CrossRefPubMedGoogle Scholar
  40. Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6:376–385CrossRefPubMedGoogle Scholar
  41. Kim YJ, Bae SW, Yu SS, Bae YC, Jung JS (2009) miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res 24:816–825CrossRefPubMedGoogle Scholar
  42. da Kim S, Lee SY, Lee JH, Bae YC, Jung JS (2015) MicroRNA-103a-3p controls proliferation and osteogenic differentiation of human adipose tissue-derived stromal cells. Exp Mol Med 47:e172CrossRefPubMedGoogle Scholar
  43. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764CrossRefPubMedGoogle Scholar
  44. Krishnan V, Bryant HU, Macdougald OA (2006) Regulation of bone mass by Wnt signaling. J Clin Invest 116:1202–1209CrossRefPubMedPubMedCentralGoogle Scholar
  45. Leboy PS (2006) Regulating bone growth and development with bone morphogenetic proteins. Ann N Y Acad Sci 1068:14–18CrossRefPubMedGoogle Scholar
  46. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419CrossRefPubMedGoogle Scholar
  47. Leucht P, Minear S, Ten Berge D, Nusse R, Helms JA (2008) Translating insights from development into regenerative medicine: the function of Wnts in bone biology. Semin Cell Dev Biol 19:434–443CrossRefPubMedGoogle Scholar
  48. Li E, Zhang J, Yuan T, Ma B (2014) MiR-143 suppresses osteogenic differentiation by targeting Osterix. Mol Cell Biochem 390:69–74CrossRefPubMedGoogle Scholar
  49. Li H, Xie H, Liu W, Hu R, Huang B, Tan YF, Xu K, Sheng ZF, Zhou HD, Wu XP, Luo XH (2009) A novel microRNA targeting HDAC5 regulates osteoblast differentiation in mice and contributes to primary osteoporosis in humans. J Clin Invest 119:3666–3677CrossRefPubMedPubMedCentralGoogle Scholar
  50. Li Y, Fan LK, Liu SY, Liu WJ, Zhang H, Zhou T, Wu D, Yang P, Shen LJ, Chen JH, Jin Y (2013) The promotion of bone regeneration through positive regulation of angiogenic–osteogenic coupling using microRNA-26a. Biomaterials 34:5048–5058CrossRefPubMedGoogle Scholar
  51. Liu H, Sun Q, Wan C, Li L, Zhang L, Chen Z (2014) MicroRNA-338-3p regulates osteogenic differentiation of mouse bone marrow stromal stem cells by targeting Runx2 and Fgfr2. J Cell Physiol 229:1494–1502CrossRefPubMedGoogle Scholar
  52. Liu J, Zheng M, Tang YL, Liang XH, Yang Q (2011) MicroRNAs, an active and versatile group in cancers. Int J Oral Sci 3:165–175CrossRefPubMedPubMedCentralGoogle Scholar
  53. Liu W, Liu Y, Guo T, Hu C, Luo H, Zhang L, Shi S, Cai T, Ding Y, Jin Y (2013) TCF3, a novel positive regulator of osteogenesis, plays a crucial role in miR-17 modulating the diverse effect of canonical Wnt signaling in different microenvironments. Cell Death Dis 4:e539CrossRefPubMedPubMedCentralGoogle Scholar
  54. Long FX (2012) Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol 13:27–38CrossRefGoogle Scholar
  55. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U (2004) Nuclear export of microRNA precursors. Science 303:95–98CrossRefPubMedGoogle Scholar
  56. Maeda S, Hayashi M, Komiya S, Imamura T, Miyazono K (2004) Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J 23:552–563CrossRefPubMedPubMedCentralGoogle Scholar
  57. Marie PJ (2008) Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys 473:98–105CrossRefPubMedGoogle Scholar
  58. Meng YB, Li X, Li ZY, Zhao J, Yuan XB, Ren Y, Cui ZD, Liu YD, Yang XJ (2015) microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/beta-catenin pathway. J Orthop Res 33:957–964CrossRefPubMedGoogle Scholar
  59. Mizuno Y, Yagi K, Tokuzawa Y, Kanesaki-Yatsuka Y, Suda T, Katagiri T, Fukuda T, Maruyama M, Okuda A, Amemiya T, Kondoh Y, Tashiro H, Okazaki Y (2008)miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation.Biochem Biophys Res Commun 368:267–272CrossRefPubMedGoogle Scholar
  60. Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondoh Y, Amemiya T, Tashiro H, Okazaki Y (2009) miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett 583:2263–2268CrossRefPubMedGoogle Scholar
  61. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108:17–29CrossRefPubMedGoogle Scholar
  62. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765–771CrossRefPubMedGoogle Scholar
  63. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147CrossRefPubMedGoogle Scholar
  64. Qiu W, Kassem M (2014) miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation. Biochim Biophys Acta 1843:2114–2121CrossRefPubMedGoogle Scholar
  65. Qu B, Xia X, Wu HH, Tu CQ, Pan XM (2014) PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 448:241–247CrossRefPubMedGoogle Scholar
  66. Rana TM (2007) Illuminating the silence: understanding the structure and function of small RNAs. Nat Rev Mol Cell Biol 8:23–36CrossRefPubMedGoogle Scholar
  67. Rebay I, Fleming RJ, Fehon RG, Cherbas L, Cherbas P, Artavanis-Tsakonas S (1991) Specific EGF repeats of Notch mediate interactions with delta and serrate: implications for Notch as a multifunctional receptor. Cell 67:687–699CrossRefPubMedGoogle Scholar
  68. Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7:885–896CrossRefPubMedGoogle Scholar
  69. Schaap-Oziemlak AM, Raymakers RA, Bergevoet SM, Gilissen C, Jansen BJ, Adema GJ, Kogler Zhang Y, Xie RL, Gordon J, LeBlanc K, Stein JL, Lian JB, van Wijnen AJ, Stein GS (2012) Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. J Biol Chem 287:21926–21935CrossRefGoogle Scholar
  70. Shi K, Lu J, Zhao Y, Wang L, Li J, Qi B, Li H, Ma C (2013) MicroRNA-214 suppresses osteogenic differentiation of C2C12 myoblast cells by targeting Osterix. Bone 55:487–494CrossRefPubMedGoogle Scholar
  71. Stein GS, Lian JB, Stein JL, van Wijnen AJ, Montecino M (1996) Transcriptional control of osteoblast growth and differentiation. Physiol Rev 76:593–629PubMedGoogle Scholar
  72. Sun J, Wang Y, Li Y, Zhao G (2014) Downregulation of PPARgamma by miR-548d-5p suppresses the adipogenic differentiation of human bone marrow mesenchymal stem cells and enhances their osteogenic potential. J Transl Med 12:168CrossRefPubMedPubMedCentralGoogle Scholar
  73. Tezuka K, Yasuda M, Watanabe N, Morimura N, Kuroda K, Miyatani S, Hozumi N (2002) Stimulation of osteoblastic cell differentiation by Notch. J Bone Miner Res 17:231–239CrossRefPubMedGoogle Scholar
  74. Tome M, Lopez-Romero P, Albo C, Sepulveda JC, Fernandez-Gutierrez B, Dopazo A, Bernad A, Gonzalez MA (2011) miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ 18:985–995CrossRefPubMedGoogle Scholar
  75. Trompeter HI, Dreesen J, Hermann E, Iwaniuk KM, Hafner M, Renwick N, Tuschl T, Wernet P (2013) MicroRNAs miR-26a, miR-26b, and miR-29b accelerate osteogenic differentiation of unrestricted somatic stem cells from human cord blood. BMC Genomics 14:111CrossRefPubMedPubMedCentralGoogle Scholar
  76. Ulsamer A, Ortuno MJ, Ruiz S, Susperregui AR, Osses N, Rosa JL, Ventura F (2008) BMP-2 induces Osterix expression through up-regulation of Dlx5 and its phosphorylation by p38. J Biol Chem 283:3816–3826CrossRefPubMedGoogle Scholar
  77. Vimalraj S, Partridge NC, Selvamurugan N (2014) A positive role of microRNA-15b on regulation of osteoblast differentiation. J Cell Physiol 229:1236–1244CrossRefPubMedPubMedCentralGoogle Scholar
  78. Vishnubalaji R, Manikandan M, Al-Nbaheen M, Kadalmani B, Aldahmash A, Alajez NM (2012) In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells. BMC Dev Biol 12:7CrossRefPubMedPubMedCentralGoogle Scholar
  79. Wan M, Cao X (2005) BMP signaling in skeletal development. Biochem Biophys Res Commun 328:651–657CrossRefPubMedGoogle Scholar
  80. Wang Q, Cai J, Cai XH, Chen L (2013) miR-346 regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting the Wnt/beta-catenin pathway. PLoS One 8:e72266CrossRefPubMedPubMedCentralGoogle Scholar
  81. Wang T, Xu Z (2010) miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochem Biophys Res Commun 402:186–189CrossRefPubMedGoogle Scholar
  82. Watanabe K, Ikeda K (2009) Osteoblast differentiation and bone formation. Nihon Rinsho 67:879–886PubMedGoogle Scholar
  83. Wei J, Shi Y, Zheng L, Zhou B, Inose H, Wang J, Guo XE, Grosschedl R, Karsenty G (2012) miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2. J Cell Biol 197:509–521CrossRefPubMedPubMedCentralGoogle Scholar
  84. Wislet-Gendebien S, Hans G, Leprince P, Rigo JM, Moonen G, Rogister B (2005) Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 23:392–402CrossRefPubMedGoogle Scholar
  85. Wu T, Xie M, Wang X, Jiang X, Li J, Huang H (2012) miR-155 modulates TNF-alpha-inhibited osteogenic differentiation by targeting SOCS1 expression. Bone 51:498–505CrossRefPubMedGoogle Scholar
  86. Xie X, Qin J, Lin SH, Tsai SY, Tsai MJ (2011) Nuclear receptor chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) modulates mesenchymal cell commitment and differentiation. Proc Natl Acad Sci U S A 108:14843–14848CrossRefPubMedPubMedCentralGoogle Scholar
  87. Xu P, Vernooy SY, Guo M, Hay BA (2003) The Drosophila microRNA Mir-14 suppresses cell death and is required for normal fat metabolism. Curr Biol 13:790–795CrossRefPubMedGoogle Scholar
  88. Yang L, Cheng P, Chen C, He HB, Xie GQ, Zhou HD, Xie H, Wu XP, Luo XH (2012) miR-93/Sp7 function loop mediates osteoblast mineralization. J Bone Miner Res 27:1598–1606CrossRefPubMedGoogle Scholar
  89. Yi R, Qin Y, Macara IG, Cullen BR (2003) Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 17:3011–3016CrossRefPubMedPubMedCentralGoogle Scholar
  90. Zeng Y, Qu X, Li H, Huang S, Wang S, Xu Q, Lin R, Han Q, Li J, Zhao RC (2012) MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2. FEBS Lett 586:2375–2381CrossRefPubMedGoogle Scholar
  91. Zhang JF, Fu WM, He ML, Wang H, Wang WM, Yu SC, Bian XW, Zhou J, Lin MC, Lu G, Poon WS, Kung HF (2011a) MiR-637 maintains the balance between adipocytes and osteoblasts by directly targeting Osterix. Mol Biol Cell 22:3955–3961CrossRefPubMedPubMedCentralGoogle Scholar
  92. Zhang JF, Fu WM, He ML, Xie WD, Lv Q, Wan G, Li G, Wang H, Lu G, Hu X, Jiang S, Li JN, Lin MC, Zhang YO, Kung HF (2011b) MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling. RNA Biol 8:829–838CrossRefPubMedGoogle Scholar
  93. Zhang J, Tu Q, Bonewald LF, He X, Stein G, Lian J, Chen J (2011c) Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1. J Bone Miner Res 26:1953–1963CrossRefPubMedGoogle Scholar
  94. Zhang WB, Zhong WJ, Wang L (2013) A signal-amplification circuit between miR-218 and Wnt/beta-catenin signal promotes human adipose tissue-derived stem cells osteogenic differentiation. Bone 58:59–66CrossRefPubMedGoogle Scholar
  95. Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ, Stein GS (2011) A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci U S A 108:9863–9868CrossRefPubMedPubMedCentralGoogle Scholar
  96. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry, College of Animal Science and TechnologyHuazhong Agricultural UniversityWuhanChina
  2. 2.The Cooperative Innovation Center for Sustainable Pig ProductionWuhanChina

Personalised recommendations