Lipoprotein Receptor-related Protein 6 Signaling is Necessary for Vasculogenic Differentiation of Human Dental Pulp Stem Cells

被引：17
作者：
Silva, Gleyce O. [1 ,2 ]
Zhang, Zhaocheng [1 ]
Cucco, Carolina [1 ]
Oh, Min [1 ]
Camargo, Carlos H. R. [2 ]
Noer, Jacques E. [1 ,3 ,4 ,5 ]
机构：
[1] Univ Michigan, Sch Dent, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA
[2] Sao Paulo State Univ, Inst Sci & Technol, Dept Restorat Dent, Sao Jose Dos Campos, SP, Brazil
[3] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Coll Engn, Dept Biomed Engn, Ann Arbor, MI 48109 USA
[5] Univ Michigan, Sch Med, Dept Otolaryngol, Ann Arbor, MI 48109 USA
来源：
JOURNAL OF ENDODONTICS | 2017年 / 43卷 / 09期
基金：
巴西圣保罗研究基金会;
关键词：
Angiogenesis; cell fate; regenerative endodontics; tissue engineering; Wnt; BETA-CATENIN; WNT; REGENERATION; PATHWAY;
D O I：
10.1016/j.joen.2017.06.006
中图分类号：
R78 [口腔科学];
学科分类号：
1003 ;
摘要：
The aim of this study was to evaluate the effects of Wnt signaling through lipoprotein receptor-related protein 6 (LRP6) and Frizzled6 on the endothelial differentiation of dental pulp stem cells (DPSCs). DPSCs were stably transduced with enhanced green fluorescent protein (EGFP) tagged lentiviral vectors (short hairpin RNA-LRP6, short hairpin RNA-Frizzled6, or empty vector controls). We evaluated the effects of LRP6 and Frizzled6 on expression of endothelial markers and on capillary tube formation mediated by DPSCs induced with recombinant human Wnt1 (rhWnt1) and/or recombinant human vascular endothelial growth factor(165) (rhVEGF(165)). In vivo, tooth slices/scaffolds were seeded with LRP6-silenced, Frizzled6-silenced, or vector control DPSC cells and transplanted into immunodeficient mice. The density of blood vessels generated by DPSCs differentiated into vascular endothelial cells was analyzed by immunohistochemistry for EGFP. The rhWnt1 and rhVEGF(165) induced expression of active beta-catenin in control DPSCs and in Frizzled6-silenced DPSCs, but not in LRP6-silenced DPSCs. Furthermore, VEGF and interleukin-8 were downregulated in LRP6-silenced DPSCs, but not in control DPSCs or in Frizzled6-silenced DPSCs (P<.05). Likewise, rhWnt1 and rhVEGF(165) induced expression of the endothelial marker VEGF receptor-2 in control DPSCs and in Frizzled6-silenced DPSCs, but not in LRP6-silenced DPSCs. These data correlated with a trend for lower density of capillary sprouts generated by LRP6-silenced DPSCs when compared with control DPSCs in Matrigel. In vivo, tooth slice/scaffolds seeded with DPSC-short hairpinRNA-LRP6 cells showed lower density of human blood vessels (ie, EGFP-positive blood vessels), when compared with tooth slice/scaffolds seeded with vector control cells (P<.05). Collectively, these data demon-strated that LRP6 signaling is necessary for the vasculogenic differentiation of human DPSCs.
引用
收藏
页码：S25 / S30
页数：6
相关论文
共 31 条
  • [11] Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo
    Gronthos, S
    Mankani, M
    Brahim, J
    Robey, PG
    Shi, S
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (25) : 13625 - 13630
  • [12] Gβγ Activates GSK3 to Promote LRP6-Mediated β-Catenin Transcriptional Activity
    Jernigan, Kristin K.
    Cselenyi, Christopher S.
    Thorne, Curtis A.
    Hanson, Alison J.
    Tahinci, Emilios
    Hajicek, Nicole
    Oldham, William M.
    Lee, Laura A.
    Hamm, Heidi E.
    Hepler, John R.
    Kozasa, Tohru
    Linder, Maurine E.
    Lee, Ethan
    [J]. SCIENCE SIGNALING, 2010, 3 (121) : ra37
  • [13] Canonical Wnt signaling is required for development of embryonic stem cell-derived mesoderm
    Lindsley, R. Coleman
    Gill, Jennifer G.
    Kyba, Michael
    Murphy, Theresa L.
    Murphy, Kenneth M.
    [J]. DEVELOPMENT, 2006, 133 (19): : 3787 - 3796
  • [14] Marco S, 2003, P NATL ACAD SCI USA, V100, P3299
  • [15] Wnt/β-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells
    Masckauchán T.N.H.
    Shawber C.J.
    Funahashi Y.
    Li C.-M.
    Kitajewski J.
    [J]. Angiogenesis, 2005, 8 (1) : 43 - 51
  • [16] A HOMOLOG OF THE ARMADILLO PROTEIN IN DROSOPHILA (PLAKOGLOBIN) ASSOCIATED WITH E-CADHERIN
    MCCREA, PD
    TURCK, CW
    GUMBINER, B
    [J]. SCIENCE, 1991, 254 (5036) : 1359 - 1361
  • [17] Effects of VEGF and FGF2 on the Revascularization of Severed Human Dental Pulps
    Mullane, E. M.
    Dong, Z.
    Sedgley, C. M.
    Hu, J. C. -C.
    Botero, T. M.
    Holland, G. R.
    Noer, J. E.
    [J]. JOURNAL OF DENTAL RESEARCH, 2008, 87 (12) : 1144 - 1148
  • [18] The application of tissue engineering to regeneration of pulp and dentin in endodontics
    Nakashima, M
    Akamine, A
    [J]. JOURNAL OF ENDODONTICS, 2005, 31 (10) : 711 - 718
  • [19] Convergence of Wnt, β-catenin, and cadherin pathways
    Nelson, WJ
    Nusse, R
    [J]. SCIENCE, 2004, 303 (5663) : 1483 - 1487
  • [20] Frizzled receptors signal through G proteins
    Nichols, Andrea S.
    Floyd, Desiree H.
    Bruinsma, Stephen P.
    Narzinski, Kirk
    Baranski, Thomas J.
    [J]. CELLULAR SIGNALLING, 2013, 25 (06) : 1468 - 1475
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