Inter J Stomatol ›› 2017, Vol. 44 ›› Issue (4): 459-465.doi: 10.7518/gjkq.2017.04.018

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Regulation of Wnt and Notch signaling pathways in the osteogenic differentiation of bone marrow-derived mesen-chymal stem cells from aged individuals

Zhang Jiankang, Wei Junjun, Tang Zhaolong, Yu Yunbo, Jing Wei   

  1. State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Dept. of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2016-12-22 Revised:2017-02-09 Online:2017-07-01 Published:2017-07-01
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81270421, 81571366).

Abstract: The impaired bone healing process in aged individuals is a common clinical problem. Bone marrow-derived mesenchymal stem cells(BMSCs), a group of pluripotent stem cells located in the bone marrow, are functional cells of new bone formation and bone metabolism. Its biological characteristics(including cell morphology, surface features, cell cycle, and level of reactive oxygen species) and proliferation and differentiation ability are varied with age, which directly affects the bone healing speed and quality at the bone injury site. Signaling pathways play a crucial role in the osteogenic differentiation of BMSCs from aged individuals. Wnt and Notch signaling pathways have been widely reported and have attracted increasing attention from the scholars in recent years. The changes of oxidative stress and growthfactors among aged individuals inhibit β-catenin activity directly by preventing β-catenin and binding its target site T cell factor and lymph enhancement factor instead of the binding fork head transcription factor and repress target gene expressions. Notch signaling pathway represses the differentiation and promotes the proliferation of BMSCs to maintain the number of BMSCs in bone marrow. The cross talk is between Notch and Wnt/β-catenin signaling pathways. Notch1 overexpression inhibits osteoblastogenesis by suppressing Wnt/β-catenin. It also plays an important role in the osteogenic differentia-tion of BMSCs from aged individuals. Moreover, the reactive oxygen species(ROS) level down-regulates bone morpho-genetic protein(BMP)-Smads and Hedgehog. Several other pathways also participate in the regulation process. This review summarizes the mechanism that Wnt/β-catenin and Notch signaling pathways regulate the osteogenic differentiation of BMSCs from aged individuals. This review may provide a new approach for the treatment of bone-related diseases in the senior population.

Key words: signaling pathway, aged, bone marrow-derived mesenchymal stem cell, osteogenesis

CLC Number: 

  • Q257

TrendMD: 
[1] Ross CL, Siriwardane M, Almeida-Porada G, et al. The effect of low-frequency electromagnetic field on human bone marrow stem/progenitor cell differentia-tion[J]. Stem Cell Res, 2015, 15(1):96-108.
[2] Lynch K, Pei M. Age associated communication between cells and matrix: a potential impact on stem cell-based tissue regeneration strategies[J]. Organo-genesis, 2014, 10(3):289-298.
[3] Yu JM, Wu X, Gimble JM, et al. Age-related chan-ges in mesenchymal stem cells derived from rhesus macaque bone marrow[J]. Aging Cell, 2011, 10(1): 66-79.
[4] Stolzing A, Jones E, McGonagle D, et al. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies[J]. Mech Ageing Dev, 2008, 129(3):163-173.
[5] Dantzer B, Fletcher QE. Telomeres shorten more slowly in slow-aging wild animals than in fast-aging ones[J]. Exp Gerontol, 2015, 71:38-47.
[6] Oh J, Lee YD, Wagers AJ. Stem cell aging: mechan-isms, regulators and therapeutic opportunities[J]. Nat Med, 2014, 20(8):870-880.
[7] Efimenko AY, Kochegura TN, Akopyan ZA, et al. Autologous stem cell therapy: how aging and chronic diseases affect stem and progenitor cells[J]. Biores Open Access, 2015, 4(1):26-38.
[8] Baxter MA, Wynn RF, Jowitt SN, et al. Study of telomere length reveals rapid aging of human mar-row stromal cells following in vitro expansion[J]. Stem Cells, 2004, 22(5):675-682.
[9] 付欣. 初步探讨自然衰老小鼠骨髓间充质干细胞生物学行为及β-catenin对其分化功能的影响[D]. 西安: 第四军医大学, 2013.
Fu X. Research on the biological function of BMMSCs from natural aging mice and the effects on the dif-ferentiation functions of β-catenin[D]. Xi’an: Fourth Military Medical University, 2013.
[10] Xiao JJ, Zhao WJ, Zhang XT, et al. Bergapten promotes bone marrow stromal cell differentiation into osteoblasts in vitro and in vivo [J]. Mol Cell Biochem, 2015, 409(1/2):113-122.
[11] Zhang W, Ou G, Hamrick M, et al. Age-related changes in the osteogenic differentiation potential of mouse bone marrow stromal cells[J]. J Bone Miner Res, 2008, 23(7):1118-1128.
[12] Leucht P, Jiang J, Cheng D, et al. Wnt3a reestab-lishes osteogenic capacity to bone grafts from aged animals[J]. J Bone Joint Surg Am, 2013, 95(14): 1278-1288.
[13] Saito-Diaz K, Chen TW, Wang X, et al. The way Wnt works: components and mechanism[J]. Growth Factors, 2013, 31(1):1-31.
[14] Niehrs C. The complex world of WNT receptor signalling[J]. Nat Rev Mol Cell Biol, 2012, 13(12): 767-779.
[15] Yu J, Virshup D. Updating the Wnt pathways[J]. Biosci Rep, 2014, 34(5):593-607.
[16] Fujimaki S, Wakabayashi T, Takemasa T, et al. The regulation of stem cell aging by Wnt signaling[J]. Histol Histopathol, 2015, 30(12):1411-1430.
[17] Acebron SP, Karaulanov E, Berger BS, et al. Mitotic Wnt signaling promotes protein stabilization and re- gulates cell size[J]. Mol Cell, 2014, 54(4):663-674.
[18] Vinyoles M, Del Valle-Pérez B, Curto J, et al. Multi-vesicular GSK3 sequestration upon Wnt signaling is controlled by p120-catenin/cadherin interaction with LRP5/6[J]. Mol Cell, 2014, 53(3):444-457.
[19] Shahnazari M, Yao W, Corr M, et al. Targeting the Wnt signaling pathway to augment bone formation [J]. Curr Osteoporos Rep, 2008, 6(4):142-148.
[20] Milovanovic P, Adamu U, Simon MJ, et al. Age- and sex-specific bone structure patterns portend bone fragility in radii and tibiae in relation to osteodensi-tometry: ahigh-resolution peripheral quantitative computed tomography study in 385 individuals[J]. J Gerontol A Biol Sci Med Sci, 2015, 70(10):1269- 1275.
[21] Ng AH, Baht GS, Alman BA, et al. Bone marrow stress decreases osteogenic progenitors[J]. Calcif Tissue Int, 2015, 97(5):476-486.
[22] Iyer S, Ambrogini E, Bartell SM, et al. FOXOs attenuate bone formation by suppressing Wnt signa-ling[J]. J Clin Invest, 2013, 123(8):3409-3419.
[23] Georgiou KR, Hui SK, Xian CJ. Regulatory path-ways associated with bone loss and bone marrow adiposity caused by aging, chemotherapy, glucocor-ticoid therapy and radiotherapy[J]. Am J Stem Cell, 2012(3):205-224.
[24] Almeida M, Han L, Martin-Millan M, et al. Oxida-tive stress antagonizes Wnt signaling in osteoblast precursors by diverting beta-catenin from T cell factor- to forkhead box O-mediated transcription[J]. J Biol Chem, 2007, 282(37):27298-27305.
[25] Guan H, Tan P, Xie L, et al. FOXO1 inhibits osteo-sarcoma oncogenesis via Wnt/β-catenin pathway suppression[J]. Oncogenesis, 2015, 4(9):e166.
[26] Schwanbeck R. The role of epigenetic mechanisms in Notch signaling during development[J]. J Cell Physiol, 2015, 230(5):969-981.
[27] Perdigoto CN, Bardin AJ. Sending the right signal: Notch and stem cells[J]. Biochim Biophys Acta, 2013, 1830(2):2307-2322.
[28] Ables JL, Decarolis NA, Johnson MA, et al. Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells[J]. J Neurosci, 2010, 30(31): 10484-10492.
[29] Watanabe K, Ikeda K. Osteoblast differentiation and bone formation[J]. Nippon Rinsho, 2009, 67(5):879- 886.
[30] Hilton MJ, Tu X, Wu X, et al. Notch signaling main-tains bone marrow mesenchymal progenitors by sup-pressing osteoblast differentiation[J]. Nat Med, 2008, 14(3):306-314.
[31] Li JL, Harris AL. Crosstalk of VEGF and Notch pathways in tumour angiogenesis: therapeutic im-plications[J]. Front Biosci(Landmark Ed), 2009, 14: 3094-3110.
[32] Zanotti S, Canalis E. Notch and the skeleton[J]. Mol Cell Biol, 2010, 30(4):886-896.
[33] Mead TJ, Yutzey KE. Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development[J]. Proc Natl Acad Sci USA, 2009, 106(34):14420-14425.
[34] Collu GM, Hidalgo-Sastre A, Brennan K. Wnt-Notch signalling crosstalk in development and disease[J]. Cell Mol Life Sci, 2014, 71(18):3553-3567.
[35] Caliceti C, Nigro P, Rizzo P, et al. ROS, Notch, and Wnt signaling pathways: crosstalk between three major regulators of cardiovascular biology[J]. Biomed Res Int, 2014, 2014:318714.
[36] Deregowski V, Gazzerro E, Priest L, et al. Notch 1 overexpression inhibits osteoblastogenesis by sup-pressing Wnt/beta-catenin but not bone morphogene-tic protein signaling[J]. J Biol Chem, 2006, 281(10): 6203-6210.
[37] Pawłowska E, Wójcik KA, Synowiec E, et al. Ex-pression of RUNX2 and its signaling partners TCF7, FGFR1/2 in cleidocranial dysplasia[J]. Acta Biochim Pol, 2015, 62(1):123-126.
[38] Collu GM, Hidalgo-Sastre A, Acar A, et al. Dishe-velled limits Notch signalling through inhibition of CSL[J]. Development, 2012, 139(23):4405-4415.
[39] Kazmers NH, McKenzie JA, Shen TS, et al. Hedge-hog signaling mediates woven bone formation and vascularization during stress fracture healing[J]. Bone, 2015, 81:524-532.
[40] Yang J, Andre P, Ye L, et al. The Hedgehog signal-ling pathway in bone formation[J]. Int J Oral Sci, 2015, 7(2):73-79.
[41] James AW. Review of signaling pathways gover-ning MSC osteogenic and adipogenic differentia-tion[J]. Scientifica, 2013, 2013:1-17.
[42] Tang Z, Wang Z, Qing F, et al. Bone morphogenetic protein Smads signaling in mesenchymal stem cells affected by osteoinductive calcium phosphate cera-mics[J]. J Biomed Mater Res A, 2015, 103(3):1001- 1010.
[43] Sharma AK, Taneja G, Khanna D, et al. Reactive oxygen species: friend or foe[J]. RSC Adv, 2015, 5 (71):57267-57276.
[44] Xie Q, Lan G, Zhou Y, et al. Strategy to enhance the anticancer efficacy of X-ray radiotherapy in me-lanoma cells by platinum complexes, the role of ROS-mediated signaling pathways[J]. Cancer Lett, 2014, 354(1):58-67.
[45] 李丽莉. BMP-Smad信号通路的调节及其在成骨分化中的作用[D]. 济南: 山东大学, 2013.
Li LL. Regulation of BMP-Smad signaling and its function in osteogenic differentiation[D]. Jinan: Shandong University, 2013.
[46] Cai JQ, Huang YZ, Chen XH, et al. Sonic Hedgehog enhances the proliferation and osteogenic differentia-tion of bone marrow-derived mesenchymal stem cells[J]. Cell Biol Int, 2012, 36(4):349-355.
[47] Regard JB, Malhotra D, Gvozdenovic-Jeremic J, et al. Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification[J]. Nat Med, 2013, 19(11):1505-1512.
[48] Kim WK, Meliton V, Bourquard N, et al. Hedgehog signaling and osteogenic differentiation in multi-potent bone marrow stromal cells are inhibited by oxidative stress[J]. J Cell Biochem, 2010, 111(5): 1199-1209.
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[9] . [J]. Foreign Med Sci: Stomatol, 2004, 31(02): 126 -128 .
[10] . [J]. Inter J Stomatol, 2008, 35(S1): .