Lipoprotein Receptor-related Protein 6 Signaling is Necessary for Vasculogenic Differentiation of Human Dental Pulp Stem Cells.
Lipoprotein Receptor-related Protein 6 Signaling is Necessary for Vasculogenic Differentiation of Human Dental Pulp Stem Cells.
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DOI：
10.1016/j.joen.2017.06.006
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发表时间：
2017-09
影响因子：
4.2
通讯作者：
Nör JE
中科院分区：
文献类型：
--
作者：
Silva GO;Zhang Z;Cucco C;Oh M;Camargo CHR;Nör JE
本研究旨在通过LRP6和Frizzled6研究Wnt信号对牙髓干细胞(DPSC)内皮细胞分化的影响。绿色荧光蛋白标记的慢病毒载体(shRNA-LRP6、shRNA-Frizzled6或空载体对照)稳定地转导DPSC。我们评价了LRP6和Frizzled6对内皮标记物表达的影响，以及对由rhWnt1和/或rhVEGF165诱导的DPSC介导的毛细血管形成的影响。在体内，牙片/支架接种LRP6沉默的、Frizzled6沉默的或载体对照的DPSC细胞，并移植到免疫缺陷小鼠体内。用免疫组织化学方法检测分化为血管内皮细胞的DPSC细胞生成的血管密度。在对照细胞和Frizzled6沉默的DPSC中，重组人WNT1和rhVEGF165诱导活性β-catenin的表达，但在LRP6沉默的DPSC中不表达。此外，在LRP6沉默的DPSC中，VEGF和IL-8表达下调，但在对照DPSC和Frizzled6沉默的DPSC中不表达(p<；0.05)。同样，在对照DPSC细胞和Frizzled6沉默的DPSC中，rhWnt1和rhVEGF165诱导内皮细胞标志物VEGFR2的表达，但在LRP6沉默的DPSC中不能。这些数据与在Matrigel中，与对照DPSC相比，LRP6沉默的DPSC细胞产生的毛细血管芽密度较低的趋势相关。在体内，与种植载体对照细胞的牙片/支架相比，种植DPSC-shRNA-LRP6细胞的牙片/支架显示出更低的人类血管密度(即EGFP阳性血管)(p<；0.05)。总之，这些数据表明，LRP6信号对人牙髓干细胞的血管生成分化是必要的。
The aim of this study is to evaluate the effects of Wnt signaling through LRP6 and Frizzled6 on the endothelial differentiation of dental pulp stem cells (DPSC). DPSC were stably transduced with EGFP-tagged lentiviral vectors (shRNA-LRP6, shRNA-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 DPSC induced with rhWnt1 and/or rhVEGF165. 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 DPSC cells differentiated into vascular endothelial cells was analyzed by immunohistochemistry for EGFP. rhWnt1 and rhVEGF165 induced expression of active-β-catenin in control DPSC cells and in Frizzled6-silenced DPSC, but not in LRP6-silenced DPSC. Further, VEGF and IL-8 were downregulated in LRP6-silenced DPSC, but not in control DPSC cells or in Frizzled6-silenced DPSC (p<0.05). Likewise, rhWnt1 and rhVEGF165 induced expression of the endothelial marker VEGFR2 in control DPSC cells and in Frizzled6-silenced DPSC, but not in LRP6-silenced DPSC. These data correlated with a trend for lower density of capillary sprouts generated by LRP6-silenced DPSC cells when compared to control DPSC in Matrigel. In vivo, tooth slice/scaffolds seeded with DPSC-shRNA-LRP6 cells showed lower density of human blood vessels (i.e. EGFP-positive blood vessels), when compared to tooth slice/scaffolds seeded with vector control cells (p<0.05). Collectively, these data demonstrated that LRP6 signaling is necessary for the vasculogenic differentiation of human dental pulp stem cells.
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影响因子：
3.7
作者：
Bronckaers A;Hilkens P;Fanton Y;Struys T;Gervois P;Politis C;Martens W;Lambrichts I
通讯作者：
Lambrichts I
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