[1] Justesen J,Stenderup K,Ebbesen EN,et al.Adipocyte tissue volume in bone marrow is increased with aging and in patients with osteoporosis.Biogerontology. 2001;2(3): 165-171.[2] Qiu W,Andersen TE,Bollerslev J,et al.Patients With High Bone Mass Phenotype Exhibit Enhanced Osteoblast Differentiation and Inhibition of Adipogenesis of Human Mesenchymal Stem Cells.J Bone Miner Res.2007;22(11): 1720-1731.[3] Forlino A,Marini JC.Osteogenesis imperfecta. Lancet.2016; 387(10028):1657-1671.[4] Pannier S,Mugniery E,Jonquoy A,et al.Delayed bone age due to a dual effect of FGFR3 mutation in Achondroplasia. Bone. 2010;47(5):905-915.[5] Alonso N,Soares DC,V McCloskey E,et al.Atypical femoral fracture in osteoporosis pseudoglioma syndrome associated with two novel compound heterozygous mutations in LRP5. J Bone Miner Res.2015;30(4):615-620.[6] Park HW,Kim YC,Yu B,et al.Alternative Wnt signaling activates YAP/TAZ.Cell. 2015;162:780-794.[7] Yuan Z,Li Q,Luo S,et al.PPARgamma and Wnt signaling in adipogenic and osteogenic differentiation of mesenchymal stem cells.Curr Stem Cell Res Ther.2015;10:1-10.[8] Hu L,Yang G,Hägg D,et al.IGF1 Promotes Adipogenesis by a Lineage Bias of Endogenous Adipose Stem/Progenitor Cells. Stem Cells.2015;33(8):2483-2495.[9] Bennett CN,Ouyang H,Ma YL,et al.Wnt10b increases postnatal bone formation by enhancing osteoblast differentiation.J Bone Miner Res.2007;22:1924-1932.[10] Stevens JR,Miranda-Carboni GA,Singer MA,et al.Wnt10b deficiency results in age-dependent loss of bone mass and progressive reduction of mesenchymal progenitor cells.J Bone Miner Res.2010;25:2138-2147.[11] Dunlap JC.Molecular bases for circadian clocks.Cell.1999; 96(2):271-290.[12] Guo B,Chatterjee S,Li L,et al.The clock gene, brain and muscle Arnt-like 1, regulates adipogenesis via Wnt signaling pathway.FASEB J.2012;26(8):3453-3463.[13] He Y,Chen Y,Zhao Q,et al.Roles of brain and muscle ARNT-like 1 and Wnt antagonist Dkk1 during osteogenesis of bone marrow stromal cells.Cell Prolif.2013;46(6):644-653.[14] Massague J.TGFbeta signalling in context.Nat Rev Mol Cell Biol.2012;13:616-630.[15] Chen G,Deng C,Li YP.TGF-beta and BMP signaling in osteoblast differentiation and bone formation.Int J Biol Sci. 2012;8:272–288.[16] Tsuji K,Bandyopadhyay A,Harfe BD,et al.BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing.Nat Genet.2006;38:1424-1429.[17] Kang 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;18:545-559.[18] Sottile V,Seuwen K.Bone morphogenetic protein-2 stimulates adipogenic differentiation of mesenchymal precursor cells in synergy with BRL 49653 (rosiglitazone).FEBS Lett.2000;475: 201-204.[19] Deng ZL,Sharff KA,Tang N,et al.Regulation of osteogenic differentiation during skeletal development.Front Biosci. 2008; 13:2001-2021.[20] Song BQ,Chi Y,Li X,et al.Inhibition of Notch signaling promotes the adipogenic differentiation of mesenchymal stem cells through autophagy activation and PTEN-PI3K/AKT/mTOR pathway.Cell Physiol Biochem.2015;36:1991-2002.[21] Deng ZL,Sharff KA,Tang N,et al.Regulation of osteogenic differentiation during skeletal development.Front Biosci.2008; 13:2001-2021.[22] Kim WK,Meliton V,Bourquard N,et al.Hedgehog signaling and osteogenic differentiation in multipotent bone marrow stromal cells are inhibited by oxidative stress.J Cell Biochem. 2010; 111:1199-1209.[23] Fontaine C,Cousin W,Plaisant M,et al.Peraldi P.Hedgehog signaling alters adipocyte maturation of human mesenchymal stem cells.Stem Cells.2008;26:1037-1046.[24] Spinella-Jaegle S,Rawadi G,Kawai S,et al.Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation.J Cell Sci.2001;114:2085-2094.[25] Togari A.Adrenergic regulation of bone metabolism: possible involvement of sympathetic innervation of osteoblastic and osteoclastic cells. Microsc Res Tech. 2002;58:77-84.[26] Hinoi E,Fujimori S,Yoneda Y.Modulation of cellular differentiation by N-methyl-D-aspartate receptors in osteoblasts. FASEB J.2003;17:1532-1534.[27] Fu L,Patel MS,Bradley A,et al.The Molecular Clock Mediates Leptin-Regulated Bone Formation.Cell.2005;122(5):803-815.[28] Eswarakumar VP,Lax I,Schlessinger J.Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev.2005;16:139-149.[29] Jackson RA,Nurcombe V,Cool SM.Coordinated fibroblast growth factor and heparin sulfate regulation of osteogenesis. Gene.2006;379:79-91.[30] Komori T.Regulation of osteoblast differentiation by transcription factors. J Cell Biochem.2006;99(5):1233-1239.[31] Franceschi RT,Xiao G.Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways.J Cell Biochem. 2003;88:446-454.[32] Otto F,Lubbert M,Stock M.Upstream and downstream targets of Runx proteins.J Cell Biochem.2003;89(1):9-18.[33] Gao RT,Zhan LP,Meng C,et al.Homeobox B7 promotes the osteogenic differentiation potential of mesenchymal stem cells by activating RUNX2 and transcript of BSP.Int J Clin Exp Med.2015;8(7):10459-10470.[34] Xu DJ,Zhao YZ,Wang J,et al.Smads,p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells.BMB Rep. 2012;45(4): 247-252. [35] Ducy P,Zhang R,Geoffroy V,et al.Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89:747-754.[36] Harada H,Tagashira S,Fujiwara M,et al.Cbfa1 isoforms exert functional differences in osteoblast differentiation.J Biol Chem. 1999;274:6972-6978.[37] Varela N,Aranguiz A,Lizama C,et al.Mitotic inheritance of mRNA facilitates translational activation of the osteogenic-lineage commitment factor Runx2 in progeny of osteoblastic cells.J Cell Physiol.2016;231(5):1001-1014.[38] Reale ME,Webb IC,Wang X,et al.The transcription factor Runx2 is under circadian control in the suprachiasmatic nucleus and functions in the control of rhythmic behavior. PLoS One.2013;8(1):e54317.[39] Zvonic S,Ptitsyn AA,Kilroy G,et al.Circadian oscillation in gene expression inmurine calvarial bone.J Bone Miner Res.2007; 22(3):357-365. [40] Dudek M,Meng QJ.Running on time: the role of circadian clocks in the musculoskeletal system.Biochem J.2014;463(1):1-8.[41] Guntur AR,Kawai M,Le P,et al.An essential role for the circadian-regulated gene nocturnin in osteogenesis: the importance of local timekeeping in skeletal homeostasis. Ann N Y Acad Sci.2011;1237:58-63.[42] McElderry JD,Zhao G,Khmaladze A,et al.Tracking circadian rhythms of bone mineral deposition in murine calvarial organ cultures.J Bone Miner Res.2013;28(8):1846-1854.[43] He Y,Lin F,Chen Y.Overexpression of the circadian clock gene Rev-erbα affects murine bone mesenchymal stem cell proliferation and osteogenesis.Stem Cells Dev.2015; 24(10): 1194-1204.[44] Samsa WE,Vasanji A,Midura RJ,et al.Deficiency of circadian clock protein BMAL1 inmice results in a low bone mass phenotype.Bone.2016;84:194-203.[45] Nakashima K,Zhou X,Kunkel G,et al.The novel zinc finger-containing transcription factor osterix is required forosteoblast differentiation and bone formation.Cell. 2002; 108(1):17-29.[46] Cheng SL,Shao JS,Charlton-Kachigian N,et al.MSX2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors.J Biol Chem.2003;278(46):45969-45977.[47] Bionaz M,Monaco E,Wheeler MB.Transcription adaptation during in vitro adipogenesis and osteogenesis of porcine mesenchymal stem cells: dy namics of pathways, biological processes, up-stream regulators, and gene networks.PLoS One.2015;10:e0137644.[48] Yu WH,Li FG,Chen XY,et al.PPARγ suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells.Int J Biochem Cell Biol. 2012;44(2): 377-384.[49] Kawai M,Green CB,Lecka-Czernik B,et al.A circadian-regulated gene, Nocturnin, promotes adipogenesis by stimulating PPAR-γ nuclear Translocation.Proc Natl Acad Sci U S A.2010;107(23):10508-10513.[50] Xing MS,Harry C,Blair M,et al.Tandem repeat of C/EBP binding sites mediates PPAR-gamma 2 gene transcription in glucocortixcoid-induce adipocyte differentiation. J Cell Biochem.2000;76:518-527.[51] Rosen ED,MacDougald OA.Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol.2006;7(12):885-896.[52] Marupanthorn K,Tantrawatpan C,Tantikanlayaporn D,et al.The effects of TNF-alpha on osteogenic differentiation of umbilical cord derived mesenchymal stem cells.J Med Assoc Thail.2015;98 Suppl 3:S34-40.[53] Muraglia A,Perera M,Verardo S,et al.DLX5 over expression impairs osteogenic differentiation of human bone mar row stromal cells. Eur J Cell Biol.2008; 87(10):751-761.[54] Choi CK,Xu Y,Wang B,et al.Substrate coupling strength of integrin-binding ligands modulates adhesion, spreading, and differentiation of human mesenchymal stem cells. Nano Lett.2015;15(10):6592-6600.[55] Fujimori K,Amano F.Forkhead transcription factor Foxa1 is a novel target gene of C/EBPbeta and suppresses the early phase of adipogenesis.Gene.2011;473(2):150-156.[56] Seifert A,Werheid DF,Knapp SM,et al. Role of Hox genes in stem cell differentiation. World J Stem Cells.2015;7(3): 583-595. [57] Han SM,Han SH,Coh YR,et al.Enhanced proliferation and differentiation of Oct4-and Sox2-over- expressing human adipose tissue mesenchymal stem cells.Exp Mol Med.2014; 46:e101.[58] Hong JH,Hwang ES,McManus MT,et al.TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005;309(5737):1074-1078. [59] Huang J,Deng F,Wang L,et al.Hypoxia induces osteogenesis-related activities and expression of core binding factor alpha1 in mesenchymal stem cells.Tohoku J Exp Med. 2011;224:7-12.[60] Hesslein DG,Fretz JA,Xi Y,et al. Ebf1-dependent control of the osteoblast and adipocyte lineages.Bone.2009;44(4):537-546.[61] Lewis BP,Burge CB,Bartel DP.Conserved seed pairing, often flanked by adenosines,indicates that thousands of human genes are microRNA targets. Cell.2005;120(1):15-20.[62] Hamam D,Ali D,Kassem M,et al. microRNAs as Regulators of Adipogenic Differentiation of Mesenchymal Stem Cells.Stem Cells Dev.2015;24(4):417-425.[63] Zhang 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.[64] Li 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.[65] Li 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.[66] Record M,Carayon K,Poirot M,et al.Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies. Biochim Biophys Acta. 2014;1841(1):108-120.[67] Baglio SR,Pegtel DM,Baldini N.Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy.Front Physiol.2012;3:359.[68] Qi X,Zhang J,Yuan H,et al.Exosomes Secreted by Human-Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Repair Critical-Sized Bone Defects through Enhanced Angiogenesis and Osteogenesis in Osteoporotic Rats.Int J Biol Sci.2016;12(7):836-849.[69] Ponting CP,Oliver PL,Reik W.Evolution and functions of long noncoding RNAs. Cell.2009;136:629-641.[70] Wang L,Wang Y,Li Z,et al.Differential expression of long noncoding ribonucleic acids during osteogenic differentiation of human bone marrow mesenchymal stem cells. Int Orthop.2015;39(5):1013-1019.[71] Huang Y,Zheng Y,Jia L,et al.Long Noncoding RNA H19 Promotes Osteoblast Differentiation Via TGF-β1/Smad3/HDAC Signaling Pathway by Deriving miR-675.Stem Cells.2015;33(12):3481-3492.[72] Huang Y,Zheng Y,Jin C,et al.Long Non-coding RNA H19 Inhibits Adipocyte Differentiation of Bone Marrow Mesenchymal Stem Cells through Epigenetic Modulation of Histone Deacetylases.Sci Rep.2016;6:28897.[73] Marie PJ,Hay E,Saidak Z.Integrin and cadherin signaling in bone: role and potential therapeutic targets.Trends Endocrinol Metab.2014;25:567-575.[74] Ge C,Yang Q,Zhao G,et al.Interactions between extracellular signal-regulated kinase 1/2 and p38 MAP kinase pathways in the control of RUNX2 phosphorylation and transcriptional activity.J Bone Miner Res.2012;27:538-551.[75] ]Marie PJ.Targeting integrins to promote bone formation and repair.Nat Rev Endocrinol.2013;9(5):288-295.[76] Taleb S,Cancello R,Clement K,et al.Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation. Endocrinology.2006;147(10): 4950-4959.[77] Kang S,Bennett CN,Gerin I,et al.Wnt signaling stimulates osteoblastogenesis of mesenchymal precursors by suppressing CCAAT/enhancerbinding protein alpha and peroxisome proliferator-activated receptor gamma.J Biol Chem.2007;282(19):14515-14524. |