The role of microRNAs in bone remodeling

Dian Jing, Jin Hao, Yu Shen, Ge Tang, Mei-Le Li, Shi-Hu Huang, Zhi-He Zhao, Dian Jing, Jin Hao, Yu Shen, Ge Tang, Mei-Le Li, Shi-Hu Huang, Zhi-He Zhao

Abstract

Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that microRNAs (miRNAs), known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression, and growing numbers of novel miRNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis, and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of miRNAs in regulating bone remodeling as well as novel applications for miRNAs in biomaterials for therapeutic purposes.

Figures

Figure 1
Figure 1
Schematic summary of miRNAs implicated in osteoblast differentiation. This figure indicates the major activities of miRNAs influencing the continuous maturation of cells from mesenchymal stromal cells to osteocytes. Selected miRNAs (purple) relative to their targets (yellow) and influencing each stage to regulate the progression of differentiation are indicated. BMP, bone morphogenetic protein.
Figure 2
Figure 2
Effects of miRNAs on osteoclast differentiation. This figure indicates the major activities of miRNAs influencing osteoclast commitment. miRNAs affect different molecular mechanisms related to this commitment, such as RANK or M-CSF receptor, among others. miRNA expression leads to alterations in osteoclast activity in vitro and changes in bone resorption in vivo. M-CSF, macrophage colony-stimulating factor; OPG, osteoprotegerin; MITF, microphthalmiaassociated transcription factor; RANK, receptor activator for nuclear factor κB; RANKL, RANK ligand; NFATc1, nuclear factor of activated T-cell calcineurin-dependent 1.

References

    1. 1Dimitriou R, Jones E, McGonagle D et al. Bone regeneration: current concepts and future directions. BMC Med 2011; 31(9): 66.
    1. 2Siddiqui NA, Owen JM. Clinical advances in bone regeneration. Curr Stem Cell Res Ther 2013; 8(3): 192–200.
    1. 3Tezuka K, Yasuda M, Watanabe N et al. Stimulation of osteoblastic cell differentiation by Notch. J Bone Miner Res 2002; 17(2): 231–239.
    1. 4Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004; 22(4): 233–241.
    1. 5Hu H, Hilton MJ, Tu X et al. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 2005; 132(1): 49–60.
    1. 6Estrada K, Styrkarsdottir U, Evangelou E et al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 2012; 44(5): 491–501.
    1. 7Zaidi SK, Young DW, Montecino M et al. Bookmarking the genome: maintenance of epigenetic information. J Biol Chem 2011; 286(21): 18355–18361.
    1. 8Ghildiyal M, Zamore PD. Small silencing RNAs: an expanding universe. Nat Rev Genet 2009; 10(2): 94–108.
    1. 9Iorio MV, Piovan C, Croce CM. Interplay between microRNAs and the epigenetic machinery: an intricate network. Biochim Biophys Acta 2010; 1799(10/11/12): 694–701.
    1. 10Sims NA, Gooi JH. Bone remodeling: multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol 2008; 19(5): 444–451.
    1. 11Schaffler MB, Cheung WY, Majeska R et al. Osteocytes: master orchestrators of bone. Calcif Tissue Int 2014; 94(1): 5–24.
    1. 12Kirk MD, Kahn AJ. Extracellular matrix synthesized by clonal osteogenic cells is osteoinductive in vivo and in vitro: role of transforming growth factor-beta 1 in osteoblast cell-matrix interaction. J Bone Miner Res 1995; 10(8): 1203–1208.
    1. 13Lien CY, Lee OK, Su Y. Cbfb enhances the osteogenic differentiation of both human and mouse mesenchymal stem cells induced by Cbfa-1 via reducing its ubiquitination-mediated degradation. Stem Cells 2007; 25(6): 1462–1468.
    1. 14Asagiri M, Takayanagi H. The molecular understanding of osteoclast differentiation. Bone 2007; 40(2): 251–264.
    1. 15Sims NA, Martin TJ. Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit. Bonekey Rep 2014; 3: 481.
    1. 16Hobert O. Gene regulation by transcription factors and microRNAs. Science 2008; 319(5871): 1785–1786.
    1. 17Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116(2): 281–297.
    1. 18Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol 2006; 13(12): 1097–1101.
    1. 19Kapinas K, Kessler CB, Delany AM. miR-29 suppression of osteonectin in osteoblasts: regulation during differentiation and by canonical Wnt signaling. J Cell Biochem 2009; 108(1): 216–224.
    1. 20Guo H, Ingolia NT, Weissman JS et al. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010; 466(7308): 835–840.
    1. 21Ambros V, Chen X. The regulation of genes and genomes by small RNAs. Development 2007; 134(9): 1635–1641.
    1. 22Cullen BR. Transcription and processing of human microRNA precursors. Mol Cell 2004; 16(6): 861–865.
    1. 23Bentwich I, Avniel A, Karov Y et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 2005; 37(7): 766–770.
    1. 24Langenberger D, Çakir MV, Hoffmann S et al. Dicer-processed small RNAs: rules and exceptions. J Exp Zool B Mol Dev Evol 2013; 320(1): 35–46.
    1. 25Dalmay T. Mechanism of miRNA-mediated repression of mRNA translation. Essays Biochem 2013; 54(1): 29–38.
    1. 26Titorencu I, Pruna V, Jinga VV et al. Osteoblast ontogeny and implications for bone pathology: an overview. Cell Tissue Res 2014; 355(1): 23–33.
    1. 27Dalle Carbonare L, Innamorati G, Valenti MT. Transcription factor Runx2 and its application to bone tissue engineering. Stem Cell Rev 2012; 8(3): 891–897.
    1. 28Ducy P, Zhang R, Geoffroy V et al. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997; 89(5): 747–754.
    1. 29Cohen MM Jr. Perspectives on RUNX genes: an update. Am J Med Genet A 2009; 149A(12): 2629–2646.
    1. 30He N, Xiao Z, Yin T et al. Inducible expression of Runx2 results in multiorgan abnormalities in mice. J Cell Biochem 2011; 112(2): 653–665.
    1. 31Ylönen R, Kyrönlahti T, Sund M et al. Type XIII collagen strongly affects bone formation in transgenic mice. J Bone Miner Res 2005; 20(8): 1381–1393.
    1. 32Huszar JM, Payne CJ. MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells. FEBS Lett 2014; 588(9): 1850–1856.
    1. 33Zhang Y, Xie RL, Croce CM 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): 9863–9868.
    1. 34Zhang Y, Xie RL, Gordon J et al. Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. J Biol Chem 2012; 287(26): 21926–21935.
    1. 35Wu T, Zhou H, Hong Y et al. miR-30 family members negatively regulate osteoblast differentiation. J Biol Chem 2012; 287(10): 7503–7511.
    1. 36Zaragosi LE, Wdziekonski B, Brigand KL 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.
    1. 37Huang J, Zhao L, Xing L et al. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 2010; 28(2): 357–364.
    1. 38Cui RR, Li SJ, Liu LJ et al. MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo. Cardiovasc Res 2012; 96(2): 320–329.
    1. 39Mizuno Y, Yagi K, Tokuzawa Y et al. miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation. Biochem Biophys Res Commun 2008; 368(2): 267–272.
    1. 40Huang K, Fu J, Zhou W et al. MicroRNA-125b regulates osteogenic differentiation of mesenchymal stem cells by targeting Cbfβ in vitro. Biochimie 2014; 102: 47–55.
    1. 41Chen S, Yang L, Jie Q et al. MicroRNA-125b suppresses the proliferation and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Mol Med Rep 2014; 9(5): 1820–1826.
    1. 42Pinto MT, Nicolete LD, Rodrigues ES et al. Overexpression of hsa-miR-125b during osteoblastic differentiation does not influence levels of Runx2, osteopontin, and ALPL gene expression. Braz J Med Biol Res 2013; 46(8): 676–680.
    1. 43Wei FL, Wang JH, Ding G et al. Mechanical force-induced specific MicroRNA expression in human periodontal ligament stem cells. Cells Tissues Organs 2014; 199(5/6): 353–363.
    1. 44Chen Y, Mohammed A, Oubaidin M et al. Cyclic stretch and compression forces alter microRNA-29 expression of human periodontal ligament cells. Gene 2015; 566(1): 13–17.
    1. 45Zuo B, Zhu J, Li J et al. microRNA-103a functions as a mechanosensitive microRNA to inhibit bone formation through targeting Runx2. J Bone Miner Res 2015; 30(2): 330–345.
    1. 46Dobreva G, Chahrour M, Dautzenberg M et al. SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 2006; 125(5): 971–986.
    1. 47Zhang J, Tu Q, Grosschedl R et al. Roles of SATB2 in osteogenic differentiation and bone regeneration. Tissue Eng Part A 2011; 17(13/14): 1767–1776.
    1. 48Tang W, Li Y, Osimiri L et al. Osteoblast-specific transcription factor Osterix (Osx) is an upstream regulator of Satb2 during bone formation. J Biol Chem 2011; 286(38): 32995–33002.
    1. 49Conner JR, Hornick JL. SATB2 is a novel marker of osteoblastic differentiation in bone and soft tissue tumours. Histopathology 2013; 63(1): 36–49.
    1. 50Hassan MQ, Gordon JA, Beloti MM 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): 19879–19884.
    1. 51Park J, Wada S, Ushida T et al. The microRNA-23a has limited roles in bone formation and homeostasis in vivo. Physiol Res 2015. [Epub ahead of print].
    1. 52Wei J, Shi Y, Zheng L et al. miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2. J Cell Biol 2012; 197(4): 509–521.
    1. 53Bae Y, Yang T, Zeng HC et al. miRNA-34c regulates Notch signaling during bone development. Hum Mol Genet 2012; 21(13): 2991–3000.
    1. 54Deng Y, Bi X, Zhou H et al. Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds. Eur Cell Mater 2014; 27: 13–24; discussion 24–25.
    1. 55Xie Q, Wang Z, Bi X et al. Effects of miR-31 on the osteogenesis of human mesenchymal stem cells. Biochem Biophys Res Commun 2014; 446(1): 98–104.
    1. 56Deng Y, Wu S, Zhou H 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): 2278–2286.
    1. 57Chen S, Feng J, Zhang H et al. Key role for the transcriptional factor, Osterix, in spine development. Spine J 2014; 14(4): 683–694.
    1. 58Nakashima K, Zhou X, Kunkel G et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002; 108(1): 17–29.
    1. 59Nishio Y, Dong Y, Paris M et al. Runx2-mediated regulation of the zinc finger Osterix/Sp7 gene. Gene 2006; 372: 62–70.
    1. 60Celil AB, Campbell PG. BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 2005; 280(36): 31353–31359.
    1. 61Matsubara T, Kida K, Yamaguchi A et al. BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem 2008; 283(43): 29119–29125.
    1. 62Baglìo SR, Devescovi V, Granchi D et al. MicroRNA expression profiling of human bone marrow mesenchymal stem cells during osteogenic differentiation reveals Osterix regulation by miR-31. Gene 2013; 527(1): 321–331.
    1. 63Yang L, Cheng P, Chen C et al. miR-93/Sp7 function loop mediates osteoblast mineralization. J Bone Miner Res 2012; 27(7): 1598–1606.
    1. 64Li E, Zhang J, Yuan T et al. MiR-143 suppresses osteogenic differentiation by targeting Osterix. Mol Cell Biochem 2014; 390(1/2): 69–74.
    1. 65Jia J, Tian Q, Ling S et al. miR-145 suppresses osteogenic differentiation by targeting Sp7. FEBS Lett 2013; 587(18): 3027–3031.
    1. 66Liu H, Lin H, Zhang L et al. miR-145 and miR-143 regulate odontoblast differentiation through targeting Klf4 and Osx genes in a feedback loop. J Biol Chem 2013; 288(13): 9261–9271.
    1. 67Zhang JF, Fu WM, He ML et al. MiR-637 maintains the balance between adipocytes and osteoblasts by directly targeting Osterix. Mol Biol Cell 2011; 22(21): 3955–3961.
    1. 68Shi K, Lu J, Zhao Y et al. MicroRNA-214 suppresses osteogenic differentiation of C2C12 myoblast cells by targeting Osterix. Bone 2013; 55(2): 487–494.
    1. 69Gámez B, Rodríguez-Carballo E, Bartrons R et al. MicroRNA-322 (miR-322) and its target protein Tob2 modulate Osterix (Osx) mRNA stability. J Biol Chem 2013; 288(20): 14264–14275.
    1. 70Chen Q, Liu W, Sinha KM et al. Identification and characterization of microRNAs controlled by the osteoblast-specific transcription factor Osterix. PLoS One 2013; 8(3): e58104.
    1. 71Chen G, Deng C, Li YP. TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 2012; 8(2): 272–288.
    1. 72Song B, Estrada KD, Lyons KM. Smad signaling in skeletal development and regeneration. Cytokine Growth Factor Rev 2009; 20(5/6): 379–388.
    1. 73Afzal F, Pratap J, Ito K et al. Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription. J Cell Physiol 2005; 204(1): 63–72.
    1. 74Kureel J, Dixit M, Tyagi AM et al. miR-542-3p suppresses osteoblast cell proliferation and differentiation, targets BMP-7 signaling and inhibits bone formation. Cell Death Dis 2014; 5: e1050.
    1. 75Luzi E, Marini F, Sala SC et al. Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor. J Bone Miner Res 2008; 23(2): 287–295.
    1. 76Xu S, Cecilia Santini G, De Veirman K et al. Upregulation of miR-135b is involved in the impaired osteogenic differentiation of mesenchymal stem cells derived from multiple myeloma patients. PLoS One 2013; 8(11): e79752.
    1. 77Li Z, Hassan MQ, Volinia S et al. A microRNA signature for a BMP2-induced osteoblast lineage commitment program. Proc Natl Acad Sci U S A 2008; 105(37): 13906–13911.
    1. 78Schaap-Oziemlak AM, Raymakers RA, Bergevoet SM et al. MicroRNA hsa-miR-135b regulates mineralization in osteogenic differentiation of human unrestricted somatic stem cells. Stem Cells Dev 2010; 19(6): 877–885.
    1. 79Li H, Li T, Wang S et al. miR-17-5p and miR-106a are involved in the balance between osteogenic and adipogenic differentiation of adipose-derived mesenchymal stem cells. Stem Cell Res 2013; 10(3): 313–324.
    1. 80Zeng Y, Qu X, Li H et al. MicroRNA-100 regulates osteogenic differentiation of human adipose-derived mesenchymal stem cells by targeting BMPR2. FEBS Lett 2012; 586(16): 2375–2381.
    1. 81Hwang S, Park SK, Lee HY et al. miR-140-5p suppresses BMP2-mediated osteogenesis in undifferentiated human mesenchymal stem cells. FEBS Lett 2014; 588(17): 2957–2963.
    1. 82Jia J, Feng X, Xu W et al. MiR-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis. Exp Mol Med 2014; 46: e107.
    1. 83Liu T, Fu NN, Song HL et al. Suppression of MicroRNA-203 improves survival of rat bone marrow mesenchymal stem cells through enhancing PI3K-induced cellular activation. IUBMB Life 2014; doi:10.1002/iub.1259. [Epub ahead of print.]
    1. 84Day TF, Guo X, Garrett-Beal L et al. Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 2005; 8(5): 739–750.
    1. 85Rossini M, Gatti D, Adami S. Involvement of WNT/β-catenin signaling in the treatment of osteoporosis. Calcif Tissue Int 2013; 93(2): 121–132.
    1. 86Liu G, Vijayakumar S, Grumolato L et al. Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells. J Cell Biol 2009; 185(1): 67–75.
    1. 87Liu W, Liu Y, Guo T et al. 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 2013; 4: e539.
    1. 88Roberto VP, Tiago DM, Silva IA et al. MiR-29a is an enhancer of mineral deposition in bone-derived systems. Arch Biochem Biophys 2014; 564: 173–183.
    1. 89Gaur T, Lengner CJ, Hovhannisyan H et al. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 2005; 280(39): 33132–33140.
    1. 90Wang J, Guan X, Guo F et al. miR-30e reciprocally regulates the differentiation of adipocytes and osteoblasts by directly targeting low-density lipoprotein receptor-related protein 6. Cell Death Dis 2013; 4: e845.
    1. 91Qiu W, Kassem M. miR-141-3p inhibits human stromal (mesenchymal) stem cell proliferation and differentiation. Biochim Biophys Acta 2014; 1843(9): 2114–2121.
    1. 92Yang X, Matsuda K, Bialek P et al. ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology; implication for Coffin-Lowry Syndrome. Cell 2004; 117(3): 387–398.
    1. 93Makowski AJ, Uppuganti S, Wadeer SA et al. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness. Bone 2014; 62: 1–9.
    1. 94Xiao G, Jiang D, Ge C et al. Cooperative interactions between activating transcription factor 4 and Runx2/Cbfa1 stimulate osteoblast-specific osteocalcin gene expression. J Biol Chem 2005; 280(35): 30689–30696.
    1. 95Liu TM, Lee EH. Transcriptional regulatory cascades in Runx2-dependent bone development. Tissue Eng Part B Rev 2013; 19(3): 254–263.
    1. 96St-Arnaud R, Mandic V. FIAT control of osteoblast activity. J Cell Biochem 2010; 109(3): 453–459.
    1. 97St-Arnaud R, Hekmatnejad B. Combinatorial control of ATF4-dependent gene transcription in osteoblasts. Ann N Y Acad Sci 2011; 1237: 11–18.
    1. 98Hekmatnejad B, Gauthier C, St-Arnaud R. Control of Fiat (factor inhibiting ATF4-mediated transcription) expression by Sp family transcription factors in osteoblasts. J Cell Biochem 2013; 114(8): 1863–1870.
    1. 99Matsuguchi T, Chiba N, Bandow K et al. JNK activity is essential for Atf4 expression and late-stage osteoblast differentiation. J Bone Miner Res 2009; 24(3): 398–410.
    1. 100Karsenty G. Transcriptional control of skeletogenesis. Annu Rev Genomics Hum Genet 2008; 9: 183–196.
    1. 101Wang X, Guo B, Li Q et al. miR-214 targets ATF4 to inhibit bone formation. Nat Med 2013; 19(1): 93–100.
    1. 102Byun MR, Kim AR, Hwang JH et al. FGF2 stimulates osteogenic differentiation through ERK induced TAZ expression. Bone 2014; 58: 72–80.
    1. 103Byun MR, Hwang JH, Kim AR et al. Canonical Wnt signalling activates TAZ through PP1A during osteogenic differentiation. Cell Death Differ 2014; 21(6): 854–863.
    1. 104Byun MR, Kim AR, Hwang JH et al. Phorbaketal A stimulates osteoblast differentiation through TAZ mediated Runx2 activation. FEBS Lett 2012; 586(8): 1086–1092.
    1. 105Jang EJ, Jeong H, Kang JO et al. TM-25659 enhances osteogenic differentiation and suppresses adipogenic differentiation by modulating the transcriptional co-activator TAZ. Br J Pharmacol 2012; 165(5): 1584–1594.
    1. 106Hong JH, Hwang ES, McManus MT et al. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science 2005; 309(5737): 1074–1078.
    1. 107Hong JH, Yaffe MB. TAZ: a beta-catenin-like molecule that regulates mesenchymal stem cell differentiation. Cell Cycle 2006; 5(2): 176–179.
    1. 108Cho HH, Shin KK, Kim YJ et al. NF-κB activation stimulates osteogenic differentiation of mesenchymal stem cells derived from human adipose tissue by increasing TAZ expression. J Cell Physiol 2010; 223(1): 168–177.
    1. 109Chaulk SG, Lattanzi VJ, Hiemer SE et al. The Hippo pathway effectors TAZ/YAP regulate dicer expression and microRNA biogenesis through Let-7. J Biol Chem 2014; 289(4): 1886–1891.
    1. 110Hao J, Zhang Y, Jing D et al. Role of Hippo signaling in cancer stem cells. J Cell Physiol 2014; 229(3): 266–270.
    1. 111Dupont S, Morsut L, Aragona M et al. Role of YAP/TAZ in mechanotransduction. Nature 2011; 474(7350): 179–183.
    1. 112Hao J, Zhang Y, Wang Y et al. Role of extracellular matrix and YAP/TAZ in cell fate determination. Cell Signal 2014; 26(2): 186–191.
    1. 113Eskildsen T, Taipaleenmäki H, Stenvang J et al. MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci U S A 2011; 108(15): 6139–6144.
    1. 114Qu B, Xia X, Wu HH et al. PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 2014; 448(3): 241–247.
    1. 115Guan X, Gao Y, Zhou J et al. miR-223 regulates adipogenic and osteogenic differentiation of mesenchymal stem cells through a C/EBPs/miR-223/FGFR2 regulatory feedback loop. Stem Cells 2015; 33(5): 1589–1600.
    1. 116Liu H, Sun Q, Wan C et al. MicroRNA-338-3p regulates osteogenic differentiation of mouse bone marrow stromal stem cells by targeting Runx2 and Fgfr2. J Cell Physiol 2014; 229(10): 1494–1502.
    1. 117Lecanda F, Warlow PM, Sheikh S et al. Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteoblast dysfunction. J Cell Biol 2000; 151(4): 931–944.
    1. 118Kim HK, Lee YS, Sivaprasad U et al. Muscle-specific microRNA miR-206 promotes muscle differentiation. J Cell Biol 2006; 174(5): 677–687.
    1. 119Inose H, Ochi H, Kimura A et al. A microRNA regulatory mechanism of osteoblast differentiation. Proc Natl Acad Sci U S A 2009; 106(49): 20794–20799.
    1. 120Itoh T, Nozawa Y, Akao Y. 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 2009; 284(29): 19272–19279.
    1. 121Sangani R, Periyasamy-Thandavan S, Kolhe R et al. MicroRNAs-141 and 200a regulate the SVCT2 transporter in bone marrow stromal cells. Mol Cell Endocrinol 2015; 410: 19–26.
    1. 122Okamoto H, Matsumi Y, Hoshikawa Y et al. Involvement of microRNAs in regulation of osteoblastic differentiation in mouse induced pluripotent stem cells. PLoS One 2012; 7(8): e43800.
    1. 123Qadir AS, Um S, Lee H et al. miR-124 negatively regulates osteogenic differentiation and in vivo bone formation of mesenchymal stem cells. J Cell Biochem 2015; 116(5): 730–742.
    1. 124Tyagi S, Gupta P, Saini AS et al. The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2011; 2(4): 236–240.
    1. 125James AW. Review of signaling pathways governing MSC osteogenic and adipogenic differentiation. Scientifica: Cairo 2013; 2013: 684736.
    1. 126Sethi JK, Vidal-Puig AJ. Thematic review series: adipocyte biology. Adipose tissue function and plasticity orchestrate nutritional adaptation. J Lipid Res 2007; 48(6): 1253–1262.
    1. 127Akune T, Ohba S, Kamekura S et al. PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 2004; 113(6): 846–855.
    1. 128Jeon MJ, Kim JA, Kwon SH et al. Activation of peroxisome proliferator-activated receptor-γ inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts. J Biol Chem 2003; 278(26): 23270–23277.
    1. 129Liu J, Wang H, Zuo Y et al. Functional interaction between peroxisome proliferator-activated receptor γ and β-catenin. Mol Cell Biol 2006; 26(15): 5827–5837.
    1. 130Zhao QH, Wang SG, Liu SX et al. PPARγ forms a bridge between DNA methylation and histone acetylation at the C/EBPα gene promoter to regulate the balance between osteogenesis and adipogenesis of bone marrow stromal cells. FEBS J 2013; 280(22): 5801–5814.
    1. 131Kang Q, Song WX, Luo Q et al. A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells. Stem Cells Dev 2009; 18(4): 545–559.
    1. 132Sun J, Wang Y, Li Y et al. Downregulation of PPARγ by miR-548d-5p suppresses the adipogenic differentiation of human bone marrow mesenchymal stem cells and enhances their osteogenic potential. J Transl Med 2014; 12: 168.
    1. 133He J, Zhang JF, Yi C et al. miRNA-mediated functional changes through co-regulating function related genes. PLoS One 2010; 5(10): e13558.
    1. 134Zhang JF, Fu WM, He ML et al. MiRNA-20a promotes osteogenic differentiation of human mesenchymal stem cells by co-regulating BMP signaling. RNA Biol 2011; 8(5): 829–838.
    1. 135Niehrs C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 2006; 25(57): 7469–7481.
    1. 136Katoh M, Katoh M. WNT signaling pathway and stem cell signaling network. Clin Cancer Res 2007; 13(14): 4042–4045.
    1. 137Zhang WB, Zhong WJ, Wang L. A signal-amplification circuit between miR-218 and Wnt/β-catenin signal promotes human adipose tissue-derived stem cells osteogenic differentiation. Bone 2014; 58: 59–66.
    1. 138Hassan MQ, Maeda Y, Taipaleenmaki H et al. miR-218 directs a Wnt signaling circuit to promote differentiation of osteoblasts and osteomimicry of metastatic cancer cells. J Biol Chem 2012; 287(50): 42084–42092.
    1. 139Zhang J, Tu Q, Bonewald LF et al. Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1. J Bone Miner Res 2011; 26(8): 1953–1963.
    1. 140van Rooij E, Sutherland LB, Thatcher JE et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proc Natl Acad Sci U S A 2008; 105(35): 13027–13032.
    1. 141Li Z, Hassan MQ, Jafferji M et al. Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 2009; 284(23): 15676–15684.
    1. 142Egea V, Zahler S, Rieth N et al. Tissue inhibitor of metalloproteinase-1 (TIMP-1) regulates mesenchymal stem cells through let-7f microRNA and Wnt/β-catenin signaling. Proc Natl Acad Sci U S A 2012; 109(6): E309–E316.
    1. 143Wang T, Xu Z. miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochem Biophys Res Commun 2010; 402(2): 186–189.
    1. 144Guo D, Li Q, Lv Q et al. MiR-27a targets sFRP1 in hFOB cells to regulate proliferation, apoptosis and differentiation. PLoS One 2014; 9(3): e91354.
    1. 145Jensen ED, Nair AK, Westendorf JJ. Histone deacetylase co-repressor complex control of Runx2 and bone formation. Crit Rev Eukaryot Gene Expr 2007; 17(3): 187–196.
    1. 146Jeon EJ, Lee KY, Choi NS et al. Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem 2006; 281(24): 16502–16511.
    1. 147Kang JS, Alliston T, Delston R et al. Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3. EMBO J 2005; 24(14): 2543–2555.
    1. 148Liu T, Hou L, Zhao Y et al. Epigenetic silencing of HDAC1 by miR-449a upregulates Runx2 and promotes osteoblast differentiation. Int J Mol Med 2015; 35(1): 238–246.
    1. 149Trompeter HI, Dreesen J, Hermann E et al. MicroRNAs miR-26a, miR-26b, and miR-29b accelerate osteogenic differentiation of unrestricted somatic stem cells from human cord blood. BMC Genomics 2013; 14: 111.
    1. 150Li H, Xie H, Liu W 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): 3666–3677.
    1. 151Hu R, Liu W, Li H et al. A Runx2/miR-3960/miR-2861 regulatory feedback loop during mouse osteoblast differentiation. J Biol Chem 2011; 286(14): 12328–12339.
    1. 152Zhang Y, Kwon S, Yamaguchi T et al. Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol Cell Biol 2008; 28(5): 1688–1701.
    1. 153Huang S, Wang S, Bian C et al. 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 2012; 21(13): 2531–2540.
    1. 154Li CJ, Cheng P, Liang MK et al. MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. J Clin Invest 2015; 125(4): 1509–1522.
    1. 155Bakhshandeh B, Hafizi M, Ghaemi N et al. Down-regulation of miRNA-221 triggers osteogenic differentiation in human stem cells. Biotechnol Lett 2012; 34(8): 1579–1587.
    1. 156Bhushan R, Grünhagen J, Becker J et al. miR-181a promotes osteoblastic differentiation through repression of TGF-β signaling molecules. Int J Biochem Cell Biol 2013; 45(3): 696–705.
    1. 157Mizuno Y, Tokuzawa Y, Ninomiya Y et al. miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett 2009; 583(13): 2263–2268.
    1. 158Cheung KS, Sposito N, Stumpf PS et al. MicroRNA-146a regulates human foetal femur derived skeletal stem cell differentiation by down-regulating SMAD2 and SMAD3. PLoS One 2014; 9(6): e98063.
    1. 159Vimalraj S, Partridge NC, Selvamurugan N. A positive role of microRNA-15b on regulation of osteoblast differentiation. J Cell Physiol 2014; 229(9): 1236–1244.
    1. 160Grünhagen J, Bhushan R, Degenkolbe E et al. MiR-497∼195 cluster microRNAs regulate osteoblast differentiation by targeting BMP signaling. J Bone Miner Res 2015; 30(5): 796–808.
    1. 161Jeong BC, Kang IH, Hwang YC et al. MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression. Cell Death Dis 2014; 5: e1532.
    1. 162Kang IH, Jeong BC, Hur SW et al. MicroRNA-302a stimulates osteoblastic differentiation by repressing COUP-TFII expression. J Cell Physiol 2015; 230(4): 911–921.
    1. 163Yang M, Pan Y, Zhou Y. miR-96 promotes osteogenic differentiation by suppressing HBEGF-EGFR signaling in osteoblastic cells. FEBS Lett 2014; 588(24): 4761–4768.
    1. 164Yu S, Geng Q, Ma J et al. Heparin-binding EGF-like growth factor and miR-1192 exert opposite effect on Runx2-induced osteogenic differentiation. Cell Death Dis 2013; 4: e868.
    1. 165Meng YB, Li X, Li ZY et al. microRNA-21 promotes osteogenic differentiation of mesenchymal stem cells by the PI3K/β-catenin pathway. J Orthop Res 2015; 33(7): 957–964.
    1. 166Karsenty G, Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2002; 2(4): 389–406.
    1. 167Del Fattore A, Teti A, Rucci N. Osteoclast receptors and signaling. Arch Biochem Biophys 2008; 473(2): 147–160.
    1. 168Mizoguchi F, Izu Y, Hayata T et al. Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. J Cell Biochem 2010; 109(5): 866–875.
    1. 169Sugatani T, Hildreth BE 3rd, Toribio RE et al. Expression of DGCR8-dependent microRNAs is indispensable for osteoclastic development and bone-resorbing activity. J Cell Biochem 2014; 115(6): 1043–1047.
    1. 170Boyce BF. Advances in the regulation of osteoclasts and osteoclast functions. J Dent Res 2013; 92(10): 860–867.
    1. 171Boyce BF. Advances in osteoclast biology reveal potential new drug targets and new roles for osteoclasts. J Bone Miner Res 2013; 28(4): 711–722.
    1. 172Liu T, Qin AP, Liao B et al. A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3). Bone 2014; 67: 156–165.
    1. 173Boyce BF, Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther 2007; 9(Suppl 1) : S1.
    1. 174Chen C, Cheng P, Xie H et al. MiR-503 regulates osteoclastogenesis via targeting RANK. J Bone Miner Res 2014; 29(2): 338–347.
    1. 175Guo LJ, Liao L, Yang L et al. MiR-125a TNF receptor-associated factor 6 to inhibit osteoclastogenesis. Exp Cell Res 2014; 321(2): 142–152.
    1. 176Lee Y, Kim HJ, Park CK et al. MicroRNA-124 regulates osteoclast differentiation. Bone 2013; 56(2): 383–389.
    1. 177Mizoguchi F, Murakami Y, Saito T et al. miR-31 controls osteoclast formation and bone resorption by targeting RhoA. Arthritis Res Ther 2013; 15(5): R102.
    1. 178Chellaiah MA, Soga N, Swanson S et al. Rho-A is critical for osteoclast podosome organization, motility, and bone resorption. J Biol Chem 2000; 275(16): 11993–12002.
    1. 179Takayanagi H, Kim S, Matsuo K et al. RANKL maintains bone homeostasis through c-Fos-dependent induction of interferon-beta. Nature 2002; 416(6882): 744–749.
    1. 180Grigoriadis AE, Wang ZQ, Cecchini MG et al. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 1994; 266(5184): 443–448.
    1. 181Sugatani T, Vacher J, Hruska KA. A microRNA expression signature of osteoclastogenesis. Blood 2011; 117(13): 3648–3657.
    1. 182Zhou Y, Liu Y, Cheng L. miR-21 expression is related to particle-induced osteolysis pathogenesis. J Orthop Res 2012; 30(11): 1837–1842.
    1. 183Sugatani T, Hruska KA. Down-regulation of miR-21 biogenesis by estrogen action contributes to osteoclastic apoptosis. J Cell Biochem 2013; 114(6): 1217–1222.
    1. 184Kim K, Kim JH, Lee J et al. MafB negatively regulates RANKL-mediated osteoclast differentiation. Blood 2007; 109(8): 3253–3259.
    1. 185Takigawa M. CCN2: a master regulator of the genesis of bone and cartilage. J Cell Commun Signal 2013; 7(3): 191–201.
    1. 186Kim K, Kim JH, Kim I et al. MicroRNA-26a regulates RANKL-induced osteoclast formation. Mol Cells 2015; 38(1): 75–80.
    1. 187Sato K, Takayanagi H. Osteoclasts, rheumatoid arthritis, and osteoimmunology. Curr Opin Rheumatol 2006; 18(4): 419–426.
    1. 188Blüml S, Bonelli M, Niederreiter B et al. Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum 2011; 63(5): 1281–1288.
    1. 189Li YT, Chen SY, Wang CR et al. Brief report: amelioration of collagen-induced arthritis in mice by lentivirus-mediated silencing of microRNA-223. Arthritis Rheum 2012; 64(10): 3240–3245.
    1. 190Sugatani T, Hruska KA. MicroRNA-223 is a key factor in osteoclast differentiation. J Cell Biochem 2007; 101(4): 996–999.
    1. 191Shibuya H, Nakasa T, Adachi N et al. Overexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation. Mod Rheumatol 2013; 23(4): 674–685.
    1. 192Pauley KM, Cha S. miRNA-146a in rheumatoid arthritis: a new therapeutic strategy. Immunotherapy 2011; 3(7): 829–831.
    1. 193Pauley KM, Satoh M, Chan AL et al. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 2008; 10(4): R101.
    1. 194Nakasa T, Miyaki S, Okubo A et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum 2008; 58(5): 1284–1292.
    1. 195Zhao Q, Shao J, Chen W et al. Osteoclast differentiation and gene regulation. Front Biosci 2007; 12: 2519–2529.
    1. 196Pixley FJ, Stanley ER. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol 2004; 14(11): 628–638.
    1. 197Mellis DJ, Itzstein C, Helfrich MH et al. The skeleton: a multi-functional complex organ: the role of key signalling pathways in osteoclast differentiation and in bone resorption. J Endocrinol 2011; 211(2): 131–143.
    1. 198Ross FP, Teitelbaum SL. αvβ3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol Rev 2005; 208: 88–105.
    1. 199Kitaura H, Kimura K, Ishida M et al. Effect of cytokines on osteoclast formation and bone resorption during mechanical force loading of the periodontal membrane. Sci World J 2014; 2014: 617032.
    1. 200Zhao C, Sun W, Zhang P et al. miR-214 promotes osteoclastogenesis by targeting Pten/PI3k/Akt pathway. RNA Biol 2015; 12(3): 343–353.
    1. 201Osta B, Benedetti G, Miossec P. Classical and paradoxical effects of TNF-α on bone homeostasis. Front Immunol 2014; 5: 48.
    1. 202Gilbert L, He X, Farmer P et al. Expression of the osteoblast differentiation factor RUNX2 (Cbfa1/AML3/Pebp2αA) is inhibited by tumor necrosis factor-α. J Biol Chem 2002; 277(4): 2695–2701.
    1. 203Huang H, Zhao N, Xu X et al. Dose-specific effects of tumor necrosis factor alpha on osteogenic differentiation of mesenchymal stem cells. Cell Prolif 2011; 44(5): 420–427.
    1. 204Gilbert LC, Chen H, Lu X et al. Chronic low dose tumor necrosis factor-α (TNF) suppresses early bone accrual in young mice by inhibiting osteoblasts without affecting osteoclasts. Bone 2013; 56(1): 174–183.
    1. 205Hah YS, Kang HG, Cho HY et al. JNK signaling plays an important role in the effects of TNF-α and IL-1β on in vitro osteoblastic differentiation of cultured human periosteal-derived cells. Mol Biol Rep 2013; 40(8): 4869–4881.
    1. 206Mukai T, Otsuka F, Otani H et al. TNF-α inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signaling. Biochem Biophys Res Commun 2007; 356(4): 1004–1010.
    1. 207Thomson BM, Mundy GR, Chambers TJ. Tumor necrosis factors alpha and beta induce osteoblastic cells to stimulate osteoclastic bone resorption. J Immunol 1987; 138(3): 775–779.
    1. 208Kitaura H, Kimura K, Ishida M et al. Immunological reaction in TNF-α-mediated osteoclast formation and bone resorption in vitro and in vivo. Clin Dev Immunol 2013; 2013: 181849.
    1. 209Kohara H, Kitaura H, Fujimura Y et al. IFN-γ directly inhibits TNF-α-induced osteoclastogenesis in vitro and in vivo and induces apoptosis mediated by Fas/Fas ligand interactions. Immunol Lett 2011; 137(1/2): 53–61.
    1. 210Wu T, Xie M, Wang X et al. miR-155 modulates TNF-α-inhibited osteogenic differentiation by targeting SOCS1 expression. Bone 2012; 51(3): 498–505.
    1. 211Zhang J, Zhao H, Chen J et al. Interferon-β-induced miR-155 inhibits osteoclast differentiation by targeting SOCS1 and MITF. FEBS Lett 2012; 586(19): 3255–3262.
    1. 212Kagiya T, Nakamura S. Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation. J Periodont Res 2013; 48(3): 373–385.
    1. 213Yang N, Wang G, Hu C et al. Tumor necrosis factor α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency-induced osteoporosis. J Bone Miner Res 2013; 28(3): 559–573.
    1. 214Dong J, Cui X, Jiang Z et al. MicroRNA-23a modulates tumor necrosis factor-alpha-induced osteoblasts apoptosis by directly targeting Fas. J Cell Biochem 2013; 114(12): 2738–2745.
    1. 215Mead TJ, Yutzey KE. Notch signaling and the developing skeleton. Adv Exp Med Biol 2012; 727: 114–130.
    1. 216Hilton MJ, Tu X, Wu X et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med 2008; 14(3): 306–314.
    1. 217Engin F, Yao Z, Yang T et al. Dimorphic effects of Notch signaling in bone homeostasis. Nat Med 2008; 14(3): 299–305.
    1. 218Yamada T, Yamazaki H, Yamane T et al. Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through stromal cells. Blood 2003; 101(6): 2227–2234.
    1. 219Chen L, Holmstrøm K, Qiu W et al. MicroRNA-34a inhibits osteoblast differentiation and in vivo bone formation of human stromal stem cells. Stem Cells 2014; 32(4): 902–912.
    1. 220Krzeszinski JY, Wei W, Huynh H et al. miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2. Nature 2014; 512(7515): 431–435.
    1. 221Palmieri A, Pezzetti F, Brunelli G et al. Differences in osteoblast miRNA induced by cell binding domain of collagen and silicate-based synthetic bone. J Biomed Sci 2007; 14(6): 777–782.
    1. 222Annalisa P, Furio P, Ilaria Z et al. Anorganic bovine bone and a silicate-based synthetic bone activate different microRNAs. J Oral Sci 2008; 50(3): 301–307.
    1. 223Deng Y, Zhou H, Gu P et al. Repair of canine medial orbital bone defects with miR-31-modified bone marrow mesenchymal stem cells. Invest Ophthalmol Vis Sci 2014; 55(9): 6016–6023.
    1. 224Wang Y, Jiang XL, Yang SC et al. MicroRNAs in the regulation of interfacial behaviors of MSCs cultured on microgrooved surface pattern. Biomaterials 2011; 32(35): 9207–9217.
    1. 225Wu K, Song W, Zhao L et al. MicroRNA functionalized microporous titanium oxide surface by lyophilization with enhanced osteogenic activity. ACS Appl Mater Interfaces 2013; 5(7): 2733–2744.
    1. 226Wu K, Xu J, Liu M et al. Induction of osteogenic differentiation of stem cells via a lyophilized microRNA reverse transfection formulation on a tissue culture plate. Int J Nanomedicine 2013; 8: 1595–1607.
    1. 227Suh JS, Lee JY, Choi YS et al. Peptide-mediated intracellular delivery of miRNA-29b for osteogenic stem cell differentiation. Biomaterials 2013; 34(17): 4347–4359.
    1. 228Qureshi AT, Monroe WT, Dasa V et al. miR-148b-nanoparticle conjugates for light mediated osteogenesis of human adipose stromal/stem cells. Biomaterials 2013; 34(31): 7799–7810.
    1. 229Liu J, Dang L, Li D et al. A delivery system specifically approaching bone resorption surfaces to facilitate therapeutic modulation of microRNAs in osteoclasts. Biomaterials 2015; 52: 148–160.
    1. 230Ding W, Li J, Singh J et al. miR-30e targets IGF2-regulated osteogenesis in bone marrow-derived mesenchymal stem cells, aortic smooth muscle cells, and ApoE−/− mice. Cardiovasc Res 2015; 106(1): 131–142.
    1. 231Wei J, Li H, Wang S et al. let-7 enhances osteogenesis and bone formation while repressing adipogenesis of human stromal/mesenchymal stem cells by regulating HMGA2. Stem Cells Dev 2014; 23(13): 1452–1463.
    1. 232Trohatou O, Zagoura D, Bitsika V et al. Sox2 suppression by miR-21 governs human mesenchymal stem cell properties. Stem Cells Transl Med 2014; 3(1): 54–68.
    1. 233Li J, He X, Wei W et al. MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1. Biochem Biophys Res Commun 2015; 460(2): 482–488.
    1. 234Kim YJ, Bae SW, Yu SS et al. miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res 2009; 24(5): 816–825.
    1. 235Guo J, Ren F, Wang Y et al. miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1 expression. J Bone Miner Res 2012; 27(7): 1607–1618.
    1. 236Dou C, Zhang C, Kang F et al. MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation. Biochim Biophys Acta 2014; 1839(11): 1084–1096.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera