脂肪来源Flk-1~+间充质干细胞自我更新相关的MicroRNA
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摘要
背景:随着干细胞研究的进展,研究者们报导了多个调节干细胞自我更新和增殖的基因,包括Oct-3/4、Sox2、c-Myc、Klf4和Lin28等。MicroRNA是一类非编码小RNA,通过后转录水平调控基因的表达。目前对MicroRNA在干细胞自我更新能力中的作用还知之甚少。目的:研究miR-Z在成体间充质干细胞分化早期的变化,为进一步探索其功能奠定基础。方法:诱导脂肪来源的间充质干细胞(AD-MSC)向神经、内皮、上皮、成骨、成脂方向分化,通过real-timePCR检测了诱导过程中miR-Z的表达变化,通过生物信息学方法预测了miR-Z的靶基因,并以成骨分化为例探讨了microRNA在抑制干细胞的“干性”促进其分化方面的功能。结果:miR-Z在AD-MSC各系分化的早期都上调,而其预测的靶基因SOX2在成脂、成骨、内皮分化的第3天均下调。结论:miR-Z可能通过抑制AD-MSC的干性起到促进其分化的作用。
Background: With advancement of stem cell research, many regulatory factors in self-renewal and proliferation of stem cells have been reported, including Oct-3/4、Sox2、c-Myc、Klf4 and Lin28. MicroRNAs are a group of small, non-encoding RNAs, functioning through post-transcriptional regulation of target genes. Few reports have been published regarding microRNA's function in self-renewal capacity of stem cell. Objective: The purpose of this study is to investigate the expression profile of miR-Z in early stage of adult mesenchymal stem cell. Methods: Human adipose-derived mesenchymal stem cells (AD-MSCs) were induced to neural, endothelial, epithelial, osteogenic, and adipogenic differentiation, during which expression profile of miR-Z was measured by real-time PCR. Osteogenesis was chosen as an example. Corresponding target genes of related microRNAs were predicted by bioinformatic method and their transcription and translation level in osteogenesis were confirmed by RTPCR and western blot, respectively. Results: The expression of miR-Z increased and peaked at Day 6-9 while mRNA of its predicted target SOX2 decreased at Day 3 during multi-lineage differentiation of AD-MSC. Conclusion: According to its characteristic expression profile, miR-Z may have an important function in regulating the sternness of AD-MSC.
引文
1 AJ Friedenstein, RK Chailakhyan, and UV Gerasimov. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet, May 1, 1987; 20(3): 263-72
    
    2 Pittenger MF, Mackay AM, Stephen CB, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284(4):143-147
    
    3 Joanna E. Grove, Emanuela Bruscia, and Diane S. Krause. Plasticity of Bone Marrow-Derived Stem Cells. Stem Cells, Jul 2004; 22: 487 - 500.
    
    4 Jiang Y, Vaessen B, Lenvik T, Blackstad M, Reyes M, Verfaillie CM: Multipotent progenitor cells can be isolated from postnatal murine bone marrow, muscle, and brain. Exp Hematol 2002, 30:896-904.
    
    5 Metcalf D: The unsolved enigmas of leukemia inhibitory factor. Stem Cells 2003, 21:5-14
    
    6 Heymann D, Rousselle AV: gp130 Cytokine family and bone cells. Cytokine 2000, 12:1455-1468.
    
    7 Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transc-optional activation in response to IFNs and other excellular signaling proteins. Science, 1994; 264(5164):1415-1421
    
    8 Niwa H, Burdon T, Chambers I, et al. Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3. Genes Dev, 1998; 12:2048-2060
    
    9 Tsutsumi S, Shimazu A, Miyazaki K, Pan H, Koike C, Yoshida E, Takagishi K, Kato Y: Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 2001, 288: 413-419.
    
    10 Zaragosi LE, Ailhaud G, Dani C: Autocrine FGF2 signaling iscritical for self-renewal of human multipotent adipose-derivedstem cells. Stem Cells 2006, 24:2412-2419
    
    11 Boland GM, Perkins G, Hall DJ, Tuan RS: Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem 2004, 93: 1210-1230
    
    12 Kleber M, Sommer L: Wnt signaling and the regulation of stem cell function. Curr Opin Cell Biol 2004, 16:681-687.
    
    13 Bienz M: The subcellular destinations of APC proteins. Nat Rev Mol Cell Biol 2002, 3:328-338.
    14 Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, et al.: Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006
    
    15 .Mitsui K, Tokuzawa Y, Itoh H, et al. The homeoprotein Nanog is required for maintenance of pluripotency in mouse epiblast and ES cells. Cell. 2003 May 30;113(5):631-42.
    
    16 Kazutoshi Takahashil and Shinya Yamanakainduction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by DefmedF actors.Cell 126, 663-676, August 25,2006
    
    17 Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J, Gimble JM, Bunnell BA: Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 2006, 99:1285-1597
    
    18 Kazutoshi Takahashi, Shinya Yamanaka. et al. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell,DOI 10.1016/j.cell.2007.11.019
    
    19 Junying Yu, James A. Thomson et al. Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells. Science, DOI: 10.1126/science.l 151526, 2007.
    
    20 Shinya Yamanaka.Strategies and New Developments in the Generation of atient-SpecificPluripotent Stem Cells.Cell Stem Cell,39-49 1, July 2007
    
    21 Yuhki Nakatake, Nobutaka Fukui, Yuko Iwamatsu, Shinji Masui, Kadue Takahashi, Rika Yagi, Kiyohito Yagi, Jun-ichi Miyazaki, Ryo Matoba, Minoru S. H. Ko, and Hitoshi Niwa. Klf4 Cooperates with Oct3/4 and Sox2 To Activate the Lefty1 Core Promoter in Embryonic Stem Cells. Mol. Cell. Biol., Oct 2006; 26: 7772 - 7782.
    
    22 Chen Y, Teng FY, Tang BL. Coaxing bone marrow stromal mesenchymal stem cells towards neuronal differentiation: progress and uncertainties. Cell Mol Life Sci. 2006 Jul;63(14):1649-57
    
    23 Donald G. Phinney and Darwin J. Prockop.Concise Review: Mesenchymal Stem/Multipotent Stromal Cells: The State of Transdifferentiation and Modes of Tissue Repair—Current Views. Stem Cells, Nov 2007; 25: 2896 - 2902
    
    24 Fang B, Liao L, Shi M et al. Multipotency of FlklCD34 progenitors derived from human fetal bone marrow. J Lab Clin Med. 2004 Apr; 143 (4) :230-40.
    
    25 Cao Y, Sun Z, Liao L et al. Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun. 2005 Jul 1;332(2):370-9.
    26 Yekta S, Shih IH, Bartel DP. MicroRNA-directed cleavage of H0XB8 mRNA. Science. 2004;304:594-596
    
    27 Giraldez AJ, Mishima Y, Rihel J, et al. Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs. Science. 2006;312:75-79.
    
    28 Zhang L, Huang J, Yang N, et al. microRNAs exhibit high frequency genomic alterations in human cancer. Proc Natl Acad Sci U S A. 2006;103:9136-9141.
    
    29 Lena AM, Shalom-Feuerstein R, di Val Cervo PR, Aberdam D, Knight RA, Melino G, Candi E. miR-203 represses 'sternness' by repressing DeltaNp63. Cell Death Differ. 2008 Jul;15(7):l 187-1195. Epub 2008 May
    
    30 Slaby O, Svoboda M, Fabian P, Smerdova T, Knoflickova D, Bednarikova M, Nenutil R, Vyzula R. Altered expression of miR-21, miR-31, miR-143 and miR-Z is related to clinicopathologic features of colorectal cancer. Oncology. 2007;72(5-6):397-402. Epub 2008 Jan 15.
    
    31 Sethupathy P, Megraw M, Hatzigeorgiou A G. A guide through present computational approaches for the identification of mammalian microRNA targets. Nat Methods, 2006, 3: 881-886
    
    32 Lewis B P, Burge C B, Bartel D P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell, 2005,120: 15-20
    
    33 Boland GM, Perkins G, Hall DJ, Tuan RS. Wnt-3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem. 2004 Dec 15; 93(6):1210-30
    
    34 de Boer J, Siddappa R, Gaspar C, van Apeldoorn A, Fodde R, van Blitterswijk C. Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells. Bone. 2004 May;34(5):818-26
    
    35 S. Leah Etheridge, Gary J. Spencer, Deborah J. Heath, and Paul G. Genever. Expression Profiling and Functional Analysis of Wnt Signaling Mechanisms in Mesenchymal Stem Cells. Stem Cells, Sep 2004; 22: 849 - 860.
    
    36 Lavery KS, Swain PM, Falb D, Alaoui-Ismaili MH. BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow derived mesenchymal stem cells. J Biol Chem. 2008 Apr 24.
    1 AJ Friedenstein, RK Chailakhyan, and UV Gerasimov. Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet, May 1, 1987; 20(3): 263-72.
    
    2 Grigoriadis AE, Heersche JN, Aubin JE. Differentiation of Muscle, Fat, Cartilage, and Bone from Progenitor Cells Present in a Bone-derived Clonal Cell Population: Effect of Dexamethasone. J Cell Biol. 1988 Jun;106(6):2139-51.
    
    3 S Wakitani, T Saito, and AI Caplan Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve, December 1, 1995; 18(12): 1417-26.
    
    4 Prockop, DJ. Marrow stromal cells as stem cells for nonhematopoietictissues. Science. 1997; 276:71-74
    
    5 Conget PA, Minguell JJ. Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 181:67-73, 1999.
    
    6 Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad. Sci U S A 1999; 96:10711-10716
    
    7 Caplan AI. The mesengenic process. Clin Plast Surg 1994; 21:429—435
    
    8 Kuznetsov SA, Friedenstein AJ, Robey PG. Factors required for bonemarrow fibroblast colony formation in vitro. Br J Haematol 1997; 97:561-570
    
    9 Pittenger MF, Mackay AM, Stephen CB, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284(4):143-147
    
    10 Planat-Benard V, Silvestre JS, Cousin B, Andre M, Nibbelink M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez M, Tedgui A, Levy B, Penicaud L, Casteilla L. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation. 2004; 109:656-663
    
    11 Nishida S, Endo N, Yamagiwa H et al. Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation. J Bone Miner Metab 1999;17:171-177.
    12 Mueller SM,Glowacki J.Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges.J Cell Biochem 2001;82:583-590.
    13 Stenderup K,Justuesen J,Clausen C et al.Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells.Bone 2003;33:919-926.
    14 Rubinstein P,Rosenfeld RE,Adamson JW et al.Stored placental blood for unrelated bone marrow reconstitution.Blood 1993;81:1679-1690
    15 Kern S,Eichler H,Stoeve J,Kl(u|¨)ter H,Bieback K.Comparative analysis of mesenchymal stem cells from bone marrow,umbilical cord blood,or adipose tissue.Stem Cells.2006 May;24(5):1294-301.Epub 2006 Jan 12
    16 Zuk PA,Zhu M,Mizuno H,Huang J,Futrell JW,Katz AJ,Benhaim P,Lorenz HP,Hedrick MH.Multilineage cells from human adipose tissue:implications for cell-based therapies.Tissue Eng.2001 Apr;7(2):211-28
    17周敦华,黄绍良.吴燕峰.等。人体间充质干细胞体外扩增及生物学特性研究[J].中华儿科杂志,2003,41(8):607
    18 De Ugarte DA,Alfonso Z,Zuk PA,etc.Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow.Immunol Lett.2003 Oct 31;89(2-3):267-70
    19 Kim HJ,Zhao Hb,Kitaura H,et al.Glucocorticoids suppress boneformation via the osteoclast[J].J Clin Invest,2006,16(8):2152
    20 Jaiswal N,Haynesworth SE,Caplan AI,et al.Osteogenic differentiation of purifield,Culture-expanded human mesenchymal stem cells in vito[J].Cell Biochem,1997,64(2):295
    21康新勤,臧伟进,胥晓丽,等.豚鼠骨髓间充质干细胞培养及向成骨细胞定向分化[J].西安交通大学学报,2004,25(2):121
    22 Zohar R,Cheifetz S,Meculloch CA,et al.Analysis of intracellular osteopontin as a marker of osteoblastic cell differentiation and mesenchymal cell migration[J].Eur J Oral Sci,1998,106(Suppl): 1401-1407
    
    23 Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2006 May; 24(5): 1294-301. Epub 2006 Jan 12
    
    24 Ogawa E, Inuzuka M, Maruyama M et al. Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Virology 1993; 194:314 -331.
    
    25 Ogawa E, Maruyama M, Kagoshima H et al. PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. Proc Natl Acad Sci U S A 1993;90:6859-6863
    
    26 Komori T. Requisite roles of Runx2 and Cbfb in skeletal development. J Bone Miner Metab 2003; 21:193-197.
    
    27 Xiao ZS, Hinson TK, Quarles LD 1999 Cbfal isoform overexpression upregulates osteocalcin gene expression in non-osteoblastic and pre-osteoblastic cells. J Cell Biochem 74:596-605
    
    28 Ducy P, Zhang R, Geoffroy V, Ridall AL, KarsentyG1997 Cbfa1/Osf2: a transcriptional activator of osteoblast differentiation. Cell 89:747-754
    
    29 Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao Y-H, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T 1997 Target disruption of Cbfal results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755-764
    
    30 Banerjee C, McCabe LR, Choi JY, Hiebert SW, Stein JL, Stein GS, Lian JB 1997 Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J Cell Biochem 66:1-8
    
    31 Ji C, Casinghino S, Chang DJ, Chen Y, Javed A, Ito Y, Hiebert SW, Lian JB, Stein GS, McCarthy TL, Centrella M 1998 CBFa (AML/PEBP2)-related elements in the TGF-b type I receptor promoter and expression with osteoblast differentiation. J Cell Biochem 69: 353-363
    
    32 Harada H, Tagashira S, Fujiwara M, Ogawa S, Katsumata T, Yamaguchi A, Komori T, NakatsukaM1999 Cbfal isoforms exert functional differences in osteoblast differentiation. J Biol Chem 274: 6972-6978
    33 Otto F, Thornell AP, Crompton T et al. Cbfal, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997:89;765-771.
    
    34 Kobayashi H, Gao Y, Ueta C et al. Multilineage differentiation of Cbfal-deficient calvarial cells in vitro. Biochem Biophys Res Commun 2000; 273:630-636.
    
    35 Wang Y, Belflower RM, Dong YF et al. Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis. J Bone Miner Res 2005;20: 1624-1636
    
    36 Zhang L, Li Z, Yan J et al. Mutagenesis of the Runt domain defines two energetic hot spots for heterodimerization with the core binding factor beta subunit. J Biol Chem 2003;278:33097-33104
    
    37 Chun-Yang Lien, Oscar K. Lee, Yeu Su et al. 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, Jun 2007; 25: 1462 -1468.
    
    38 K Nakashima, X Zhou, G Kunkel, Z Zhang, JM Deng, RR Behringer, and B de Crombrugghe. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell, Jan 2002; 108(1): 17-29.
    
    39 Kannan Thirunavukkarasu, Muktar Mahajan, Keith W. McLarren, Stefano Stifani, and Gerard Karsenty. Two Domains Unique to Osteoblast-Specific Transcription Factor Osf2/Cbfa1 Contribute to Its Transactivation Function and Its Inability To Heterodimerize with Cbfβ. Mol. Cell. Biol., Jul 1998; 18: 4197 - 4208.
    
    40 K Thirunavukkarasu, RR Miles, DL Halladay, and JE Onyia. Cryptic enhancer elements in luciferase reporter vectors respond to the osteoblast-specific transcription factor Osf2/Cbfa1. Biotechniques, Mar 2000; 28(3): 506-10.
    
    41 Kawabata M, Imamura T, Miyazono K. Signal transduction by bone morphogenetic proteins. Cytokine Growth Factor Rev. 1998 Mar; 9(1): 49-61.
    
    42 Wordinger RJ, Clark AF. Bone morphogenetic proteins and their receptors in the eye. Exp Biol Med (Maywood). 2007 Sep; 232(8): 979-92
    
    43 Ghosh-Choudhury N, Harris MA, Feng JQ, Mundy GR, Harris SE. Expression of the BMP 2 gene during bone cell differentiation. Crit Rev Eukaryot Gene Expr 1994 4:345-355
    44 Boden SD,Hair G,Titus L,Racine M,McCuaig K,Wozney JM,Nanes MS.Glucocorticoid-induced differentiation of fetal rat calvarial osteoblasts is mediated by bone morphogenetic protein-6.Endocrinology 1997 138:2820-2828
    45 Hughes FJ,Collyer J,Stanfield M,Goodman SA.The effects of bone morphogenetic protein-2,-4,and -6 on differentiation of rat osteoblast cells in vitro.Endocrinology 1995 136:2671-2677
    46 Thies RS,Bauduy M,Ashton BA,Kurtzberg L,Wozney JM,Rosen V.Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells.Endocrinology 1992 130:1318-1324
    47 Reddi AH.Bone morphogenetic proteins:from basic science to clinical applications [J].J Bone Joint Surg Am,2001,83-A Suppl 1(Pt1):S1-6
    48 Lavery KS,Swain PM,Falb D,Alaoui-Ismaili MH.BMP-2/4 and BMP-6/7differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow derived mesenchymal stem cells.J Biol Chem.2008 Apr 24
    49 Nohe A,Hassel S,Ehrlich M,Neubauer F,Sebald W,Henis YI,Knaus P.The mode of bone morphogenetic protein(BMP) receptor oligomerization determines different BMP-2 signaling pathways.J Biol Chem 2002 277:5330-5338
    50 Kretzschmar M,Massague J.Smads:mediators and regulators of TGF-βsignaling.Curr Opin Genet Dev 1998 8:103-111
    51 Derynck R,Zhang Y,Feng X-H.Smads:transcriptional activators of TGF-βresponses.Cell 1998 95:737-740
    52 Kawabata M,Imamura T,Miyazono K.Signal transduction by bone morphogenetic proteins.Cytokine Growth Factor Rev 1998 9:49-61
    53 LeSueur JA,Graft JM Spemann organizer activity of Smad 10.Development 1999126:137-146
    54 Miyazono K.Signal transduction by bone morphogenetic protein receptors:functional roles of Smad proteins.Bone 1999 25:91-93
    55 Shi X,Yang X,Chen D,Chang Z,Cao X Smad 1 interacts with homeobox DNA-binding proteins in bone morphogenetic protein signaling.J Biol Chem 1999274:13711-13717
    56 Lee K-S, Kim H-J, Li Q-L, Chi X-Z, Ueta C, Komori T, Wozney JM, Kim E-G, Choi J-Y, Ryoo H-M, Bae S-C Runx2 is a common target of transforming growth factor _1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol 2000 20:8783-8792
    
    57 Zaidi SK, Sullivan AJ, van Wijnen AJ, Stein JL, Stein GS, Lian JB 2002 Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proc Natl Acad Sci USA 99: 8048-8053
    
    58 Attisano L, Wrana JL 2002 Signal transduction by the TGF-P superfamily. Science 296:1646-1647 150.
    
    59 L. Bryan Ray and Thomas W. Sturgill. Rapid Stimulation by Insulin of a Serine/Threonine Kinase in 3T3-L1 Adipocytes that Phosphorylates Microtubule-Associated Protein 2 in vitro. PNAS, Mar 1987; 84: 1502 - 1506
    
    60 Marshall CJ. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation
    
    61 Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC. Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction. J Cell Sci. 1995 Nov;108 ( Pt 11):3599-609
    
    62 Weston CR, Lambright DG, Davis RJ. MAP kinase signaling specificity. Science 2002 296:2345-2347
    
    63 Lai C-F, Cheng S-L 2002 Signal transduction induced by bone morphogenetic protein-2 and transforming growth factor-_ in normal human osteoblastic cells. J Biol Chem 277:15514-15522
    
    64 Jaiswal RK, Jaiswal N, Binder SP, Mbalaviele G, Marshak DR, Pittenger MF. Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem. 2000 Mar 31;275(13):9645-52
    
    65 Akiyama T. Wnt/beta-catenin signaling. Cytokine Growth Factor Rev 2000; 11:273-282
    
    66 Takemaru KI, Moon RT. The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J Cell Biol. 2000; 149: 249-254.
    
    67 Hecht A, Vleminckx K, Stemmler MP, van Roy F, Kemler R. The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J . 2000; 19: 1839-1850
    
    68 de Boer J, Siddappa R, Gaspar C, van Apeldoorn A, Fodde R, van Blitterswijk C. Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells. Bone. 2004 May;34(5):818-26.
    
    69 Boland GM, Perkins G, Hall DJ, Tuan RS. Wnt-3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells. J Cell Biochem. 2004 Dec 15; 93(6): 1210-30
    
    70 S. Leah Etheridge, Gary J. Spencer, Deborah J. Heath, and Paul G. Genever. Expression Profiling and Functional Analysis of Wnt Signaling Mechanisms in Mesenchymal Stem Cells. Stem Cells, Sep 2004; 22: 849 - 860.
    
    71 MT Veeman, JD Axelrod, and RT Moon. A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling. Dev Cell, Sep 2003; 5(3): 367-77
    
    72 Wen Luo, Wilson W. Ng, Li-Hua Jin, Zhiyun Ye, Jiahuai Han, and Sheng-Cai Lin. Axin Utilizes Distinct Regions for Competitive MEKK1 and MEKK4 Binding and JNK Activation. J. Biol. Chem., Sep 2003; 278: 37451 - 37458
    
    73 R Habas, Y Kato, and X He. Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell, Dec 2001; 107(7): 843-54.
    
    74 Chang J, Sonoyama W, Wang Z, Jin Q, Zhang C, Krebsbach PH, Giannobile W, Shi S, Wang CY. Noncanonical Wnt-4 signaling enhances bone regeneration of mesenchymal stem cells in craniofacial defects through activation of p38 MAPK. J Biol Chem. 2007 Oct 19; 282(42): 30938-48. Epub 2007 Aug 24
    
    75 Ryuji Ikeda, Kenichi Yoshida, So Tsukahara, Yoshiko Sakamoto, Hiroshi Tanaka, Ken-Ichi Furukawa, and Ituro Inoue. The Promyelotic Leukemia Zinc Finger Promotes Osteoblastic Differentiation of Human Mesenchymal Stem Cells as an Upstream Regulator of CBFA1. J. Biol. Chem., Mar 2005; 280: 8523 - 8530.
    
    76 Guozhi Xiao, Di Jiang, Rajaram Gopalakrishnan, and Renny T. Franceschi. Fibroblast Growth Factor 2 Induction of the Osteocalcin Gene Requires MAPK Activity and Phosphorylation of the Osteoblast Transcription Factor, Cbfa1/Runx2. J. Bio 1. Chem., Sep 2002; 277: 36181 - 36187.
    
    77 HJ Wee, G Huang, K Shigesada, and Y Ito. Serine phosphorylation of RUNX2 with novel potential functions as negative regulatory mechanisms. EMBO Rep, Oct 2002; 3(10): 967-74.
    
    78 Yin Tintut, Farhad Parhami, Vien Le, Gerard Karsenty, and Linda L. Demer . Inhibition of Osteoblast-specific Transcription Factor Cbfa1 by the cAMP Pathway in Osteoblastic Cells. UBIQUITIN/PROTEASOME-DEPENDENT REGULATION. J. Biol. Chem., Oct 1999; 274: 28875
    
    79 DM Thomas, SA Carty, DM Piscopo, JS Lee, WF Wang, WC Forrester, and PW Hinds . The retinoblastoma protein acts as a transcriptional coactivator required for os teogenic differentiation. Mol Cell, Aug 2001; 8(2): 303-16
    
    80 I Satokata, L Ma, H Ohshima, M Bei, I Woo, K Nishizawa, T Maeda, Y Takano, M Uchiyama, S Heaney, H Peters, Z Tang, R Maxson, and R Maas. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet, Apr 2000; 24(4): 391-5.
    
    81 Mi-Hye Lee, Youn-Jeong Kim, Hyun-Jung Kim, Hyun-Dong Park, Ae-Ree Kang, Hee-Moon Kyung, Jae-Hyun Sung, John M. Wozney, Hyun-Jung Kim, and Hyun-Mo Ryoo. BMP-2-induced Runx2 Expression Is Mediated by Dlx5, and TGF-β1 Opposes the BMP-2-induced Osteoblast Differentiation by Suppression of Dlx5 Expression. J. Biol. Chem., Sep 2003; 278: 34387 - 34394.
    
    82 Ernesto Canalis, Aris N. Economides, and Elisabetta Gazzerro. Bone Morphogenetic Proteins, Their Antagonists, and the Skeleton. Endocr. Rev., Apr 2003; 24:218
    
    83 Mariani FV, Harland RM. XBF-2 is a transcriptional repressor that converts ectoderm into neural tissue. Development 1998 125:5019-5031
    
    84 Cornell CN, Lane JM. Newest factors in fracture healing. [ J ]. Clin Or2 thop, 1992, (277) :2972311.
    
    86 Zaidi SK, Sullivan AJ, van Wijnen AJ, Stein JL, Stein GS, Lian. JB 2002 Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proc Natl Acad Sci USA 99: 8048-8053
    
    87 Bonewald LF,Mundy GR. Role of transforming growth factor2beta in bone remodeling[ J . Clin Orthop, 1990, (250): 2612276.
    
    88 Jaiswal N, Haynesworth SE, Cap lan A I, et al. Osteogenic differentia2 tion of purified, culture2expanded human mesenchymal stem cells in vitro[ J ]. J Cell Biochem, 1997, 64 (2): 2952312.
    
    89 Locklin RM, Williamson MC, Beresford JN, et al. In vitro effects of growth factors and dexamethasone on rat marrow stromal cells[ J ]. Clin Orthop, 1995, (313): 27235
    
    90 Feng-Sheng Wang, Ching-Jen Wang, Shyr-Ming Sheen-Chen, Yur-Ren Kuo, Rong-Fu Chen, and Kuender D. Yang, Superoxide Mediates Shock Wave Induction of ERK-dependent Osteogenic Transcription Factor (CBFA1) and Mesenchymal Cell Differentiation toward Osteoprogenitors. J. Biol. Chem., Mar 2002; 277: 10931 -10937.
    
    91 Moyzis RK, Buckingham JM, Cram LS et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A 1988; 85:6623-6626
    
    92 Soo Kyung Kang, Lorna Putnam, Jason Dufour, Joni Ylostalo, Jin Sup Jung, and Bruce A. Bunnell. Expression of Telomerase Extends the Lifespan and Enhances Osteogenic Differentiation of Adipose Tissue-Derived Stromal Cells. Stem Cells, Dec 2004; 22: 1356-1372.
    
    93 Shan Sun, Yaoming Liu, Samantha Lipsky, and Michael Cho. Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cells. FASEB J, May 2007; 21: 1472 -1480.
    
    94 Majd Zayzafoon, William E. Gathings, and Jay M. McDonald. Modeled Micrograviry Inhibits Osteogenic Differentiation of Human Mesenchymal Stem Cells and Increases Adipogenesis. Endocrinology, May 2004; 145: 2421 - 2432
    
    95 Ali Salim, Randall P. Nacamuli, Elise F. Morgan, Amato J. Giaccia, and Michael T. Longaker. Transient Changes in Oxygen Tension Inhibit Osteogenic Differentiation and Runx2 Expression in Osteoblasts. J. Biol. Chem., Sep 2004; 279: 40007 - 40016.

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