Wnt/β-catenin inhibits dental pulp stem cell differentiation
Wnt/β-catenin inhibits dental pulp stem cell differentiation
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DOI：
10.1177/154405910808700206
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发表时间：
2008-02-01
影响因子：
7.6
通讯作者：
Wang, C. Y.
中科院分区：
文献类型：
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作者：
Scheller, E. L.;Chang, J.;Wang, C. Y.
牙髓干细胞（DPSCs）是从出生后的人牙髓中分离的独特的前体细胞群，具有再生修复性牙本质样复合体的能力。典型的Wnt信号通过β-连环蛋白在牙齿发育和干细胞自我更新中起着关键作用。在这项研究中，典型的Wnt信号转导的成牙本质细胞样分化的DPSCs的调节进行了检查。DPSC稳定转导经典Wnt-1或β-连环蛋白的活性形式，逆转录病毒介导的感染。北方印迹分析发现，Wnt-1可显著诱导DPSC中基质细胞蛋白骨桥蛋白的表达，并适度促进I型胶原的表达。出乎意料的是，Wnt-1抑制碱性磷酸酶（ALP）的活性和矿化结节的形成DPSC。此外，β-连环蛋白的过表达也足以抑制DPSC的分化和矿化。总之，我们的研究结果表明，典型的Wnt信号负调控成牙本质细胞样分化的DPSCs。所用缩写：DPSC，牙髓干细胞; ALP，碱性磷酸酶; BSP，骨唾液蛋白; MSC，间充质干细胞; β-GP，β-甘油磷酸盐; APC，结肠腺瘤性息肉病; GSK-3 β，糖原合成酶激酶-3 β; LRP，LDL受体相关蛋白; Tcf，T细胞因子; LEF，淋巴增强因子; FCS，胎牛血清; AA，L-抗坏血酸2-磷酸盐; α-MEM，α-改良Eagle培养基; PBS，磷酸盐缓冲盐水; HA，血凝素; ON，骨连接蛋白; OPN，骨桥蛋白。
Dental pulp stem cells (DPSCs) are a unique precursor population isolated from post-natal human dental pulp and have the ability to regenerate a reparative dentin-like complex. Canonical Wnt signaling plays a critical role in tooth development and stem cell self-renewal through beta-catenin. In this study, the regulation of odontoblast-like differentiation of DPSCs by canonical Wnt signaling was examined. DPSCs were stably transduced with canonical Wnt-1 or the active form of beta-catenin, with retrovirus-mediated infection. Northern blot analysis found that Wnt-1 strongly induced the expression of matricellular protein osteopontin, and modestly enhanced the expression of type I collagen in DPSCs. Unexpectedly, Wnt-1 inhibited alkaline phosphatase (ALP) activity and the formation of mineralized nodules in DPSCs. Moreover, overexpression of beta-catenin was also sufficient to suppress the differentiation and mineralization of DPSCs. In conclusion, our results suggest that canonical Wnt signaling negatively regulates the odontoblast-like differentiation of DPSCs. Abbreviations used: DPSC, dental pulp stem cell; ALP, alkaline phosphatase; BSP, bone sialoprotein; MSC, mesenchymal stem cell; beta-GP, beta-glycerophosphate; APC, adenomatous polyposis coli; GSK-3 beta, glycogen synthase kinase-3 beta; LRP, LDL receptor-related protein; Tcf, T-cell factor; LEF, lymphoid enhancer factor; FCS, fetal calf serum; AA, L-ascorbic acid 2-phosphate; alpha-MEM, alpha-modified Eagle's medium; PBS, phosphate-buffered saline; HA, hemagglutinin; ON, osteonectin; OPN, osteopontin.