N-Cadherin Regulates the Odontogenic Differentiation of Dental Pulp Stem Cells via β-Catenin Activity.
N-Cadherin Regulates the Odontogenic Differentiation of Dental Pulp Stem Cells via β-Catenin Activity.
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DOI：
10.3389/fcell.2021.661116
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhao W
中科院分区：
文献类型：
--
作者：
Deng Z;Yan W;Dai X;Chen M;Qu Q;Wu B;Zhao W
牙髓干细胞(DPSC)移植在牙髓再生方面显示出新的前景，在牙髓炎和牙髓坏死的治疗中具有重要意义。干细胞的命运和再生能力在很大程度上取决于其微环境，微环境由各种组织成分、细胞群体和可溶性因子组成。N-钙粘附素介导的细胞-细胞相互作用被认为是控制间充质干细胞细胞命运承诺的重要因素。本研究采用细胞培养模型和小鼠皮下移植模型，研究了N-钙粘附素在体外和体内对牙源性牙源性干细胞分化的影响及其可能的机制。研究发现，在DPSCs的分化过程中，N-钙粘蛋白的表达与牙源性标志物(牙本质涎磷蛋白和矮小相关转录因子2)的表达呈负相关。特异性shRNA下调DPSCs中N-钙粘蛋白的表达可显著增加DSPP和Runx2的表达，增强碱性磷酸酶(ALP)活性，促进矿化结节的形成。值得注意的是，N-钙粘附素沉默促进了细胞核移位和β-连环素的积累。用特异性抑制剂XAV939抑制β-catenin，可逆转N-钙粘素下调对牙源性干细胞分化的促进作用。此外，N-钙粘附素基因敲除促进了β-磷酸三钙/DPSCs复合材料移植到小鼠体内的成牙本质细胞样细胞和胶原基质的形成。综上所述，N-钙粘附素在牙髓干细胞牙源性分化过程中通过调节β-连环蛋白的活性发挥负性调节作用。这些数据可能有助于通过调节N-钙粘附素介导的细胞-细胞相互作用来指导DPSC的行为，并对牙髓再生产生影响。
Dental pulp stem cell (DPSC) transplantation has shown new prospects in dental pulp regeneration, and is of great significance in the treatment of pulpitis and pulp necrosis. The fate and regenerative potential of stem cells are dependent, to a great extent, on their microenvironment, which is composed of various tissue components, cell populations, and soluble factors. N-cadherin-mediated cell–cell interaction has been implicated as an important factor in controlling the cell-fate commitment of mesenchymal stem cells. In this study, the effect of N-cadherin on odontogenic differentiation of DPSCs and the potential underlying mechanisms, both in vitro and in vivo, was investigated using a cell culture model and a subcutaneous transplantation mouse model. It was found that the expression of N-cadherin was reversely related to the expression of odontogenic markers (dentin sialophosphoprotein, DSPP, and runt-related transcription factor 2, Runx2) during the differentiation process of DPSCs. Specific shRNA-mediated knockdown of N-cadherin expression in DPSCs significantly increased the expression of DSPP and Runx2, alkaline phosphatase (ALP) activity, and the formation of mineralized nodules. Notably, N-cadherin silencing promoted nucleus translocation and accumulation of β-catenin. Inhibition of β-catenin by a specific inhibitor XAV939, reversed the facilitating effects of N-cadherin downregulation on odontogenic differentiation of DPSCs. In addition, knockdown of N-cadherin promoted the formation of odontoblast-like cells and collagenous matrix in β-tricalcium phosphate/DPSCs composites transplanted into mice. In conclusion, N-cadherin acted as a negative regulator via regulating β-catenin activity during odontogenic differentiation of DPSCs. These data may help to guide DPSC behavior by tuning the N-cadherin-mediated cell–cell interactions, with implications for pulp regeneration.
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影响因子：
4.2
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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