Age-Dependent Impaired Neurogenic Differentiation Capacity of Dental Stem Cell is Associated with Wnt/β-Catenin Signaling
Age-Dependent Impaired Neurogenic Differentiation Capacity of Dental Stem Cell is Associated with Wnt/β-Catenin Signaling
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DOI：
10.1007/s10571-013-9965-0
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发表时间：
2013-11-01
影响因子：
4
通讯作者：
Li, Liren
中科院分区：
文献类型：
--
作者：
Feng, Xingmei;Xing, Jing;Li, Liren
牙髓干细胞（DPSCs）和人脱落乳牙干细胞（SHED）是一种新型的间充质干细胞，可以在体外诱导分化为成骨细胞、软骨细胞、脂肪细胞和神经元样细胞。我们知道，它们都起源于神经嵴，但在体外和体内具有不同的特征和功能。随着年龄的增长，dsc的再生潜力下降；然而，对DSCs中电位受损的机制尚未充分探讨。在这项研究中，我们研究了神经源性分化能力的下降是否与体外Wnt信号相关蛋白的表达改变有关。我们比较了从两个年龄组的人牙髓中分离的干细胞：脱落的乳牙（5-12岁）和第三恒牙（45-50岁）。我们发现，与SHED组相比，DPSCs组神经元标志物β iii -微管蛋白、微管相关蛋白2（MAP2）、酪氨酸羟化酶（TH）和Nestin的表达水平较低；然而，在培养基中添加人重组Wnt1后，DPSCs倾向于神经分化，并表达更高水平的神经源性标志物。总之，我们的研究表明Wnt/ β -catenin信号可能在dsc的年龄依赖性神经分化中发挥重要作用。因此，dsc可能提供一个理想的干细胞来源，可以进一步扩大其在神经损伤和神经退行性疾病的治疗应用。
Two kinds of dental stem cells (DSCs), dental pulp stem cells (DPSCs) and stem cells from human-exfoliated deciduous teeth (SHED), have been identified as novel populations of mesenchymal stem cells that can be induced to differentiate into osteoblasts, chondrocytes, adipocytes, and neuron-like cells in vitro. As we know, both of them originate from the neural crest, but have distinct characteristics and functions in vitro and in vivo. The regeneration potential of DSCs declines with advanced age; however, the mechanism of the impaired potential in DSCs has not been fully explored. In this study, we investigated whether declined neurogenic differentiation capacity is associated with an altered expression of Wnt signaling-related proteins in vitro. We compared stem cells isolated from human dental pulp in two age groups: the exfoliated deciduous teeth (5-12 years), and the third permanent teeth (45-50 years). We found that the expression levels of neuron markers, such as beta III-tubulin, microtubule-associated protein 2(MAP2), tyrosine hydroxylase (TH), and Nestin were lower in the DPSCs group compared with that in the SHED group; however, in supplementation with human recombinant Wnt1 in the medium, the DPSCs were prone to neural differentiation and expressed higher levels of neurogenic markers. In summary, our study demonstrated that Wnt/beta-catenin signaling may play a vital role in the age-dependent neural differentiation of DSCs. Therefore, DSCs may provide an ideal source of stem cells that can further extend their therapeutic application in nerve injury and neurodegenerative diseases.