Enamel Matrix Derivative Enhances the Odontoblastic Differentiation of Dental Pulp Stem Cells via Activating MAPK Signaling Pathways.

Enamel Matrix Derivative Enhances the Odontoblastic Differentiation of Dental Pulp Stem Cells via Activating MAPK Signaling Pathways.
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牙釉质基质衍生物通过激活 MAPK 信号通路增强牙髓干细胞的成牙本质细胞分化

DOI:
10.1155/2022/2236250
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发表时间:
2022
影响因子:
4.3
通讯作者:
Qiu, Lihong
Qiu, Lihong
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Beidi;Xiao, Min;Cheng, Xiaogang;Bai, Yu;Chen, Hanze;Yu, Qing;Qiu, Lihong

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牙髓干细胞向成牙本质细胞分化有助于牙髓牙本质再生。牙釉质基质衍生物(Enamel matrix derivative,EMD)是牙胚发育过程中诱导细胞分化的重要上皮信号,已广泛应用于临床牙周组织再生。本研究旨在探讨EMD对DPSCs增殖和向成牙本质细胞分化的影响及其可能机制。我们进行了体外和体内研究,以获得对EMD的全面了解。体外阶段:采用CCK-8法检测成牙本质细胞的增殖情况,并通过碱性磷酸酶(ALP)活性检测、茜素红染色、实时荧光定量RT-PCR和western blot检测成牙本质细胞分化潜能和MAPK信号通路的参与情况。体内阶段:在通过扫描电子显微镜(SEM)确定VitroGel 3D-RGD的生物相容性之后,将水凝胶混合物皮下注射到裸鼠中,随后进行组织学和免疫组织化学分析。结果表明,EMD在体外和体内均能促进DPSCs向成牙本质细胞分化,但不影响DPSCs的增殖。阻断MAPK通路可抑制EMD诱导的DPSCs分化。VitroGel 3D-RGD对DPSCs的增殖、分化和再生具有良好的支持作用。总之,本研究表明EMD通过触发MAPK信号通路促进DPSCs向成牙本质细胞分化。这些发现为EMD影响DPSC分化的机制提供了新的见解,并提出EMD作为未来干细胞治疗牙髓病的有希望的候选者。
The odontoblastic differentiation of dental pulp stem cells (DPSCs) contributes to pulp-dentin regeneration. Enamel matrix derivative (EMD) is considered to be a critical epithelial signal to induce cell differentiation during odontogenesis and has been widely applied to clinical periodontal tissue regeneration. The purpose of this study was to explore the effect of EMD on DPSCs proliferation and odontoblastic differentiation, as well as the underlying mechanisms. We conducted in vitro and in vivo researches to get a comprehensive understanding of EMD. In vitro phase: cell proliferation was assessed by a cell counting kit-8 (CCK-8) assay; then, alkaline phosphatase (ALP) activity and staining, alizarin red staining, real-time RT-PCR, and western blot analysis were conducted to determine the odontoblastic potential and involvement of MAPK signaling pathways. In vivo phase: after ensuring the biocompatibility of VitroGel 3D-RGD via scanning electron microscopy (SEM), the hydrogel mixture was subcutaneously injected into nude mice followed by histological and immunohistochemical analyses. The results revealed that EMD did not interfere with DPSCs proliferation but promoted the odontoblastic differentiation of DPSCs in vitro and in vivo. Furthermore, blocking the MAPK pathways suppressed the EMD-enhanced differentiation of DPSCs. Finally, VitroGel 3D-RGD could well support the proliferation, differentiation, and regeneration of DPSCs. Overall, this study demonstrates that EMD enhances the odontoblastic differentiation of DPSCs through triggering MAPK signaling pathways. The findings provide a new insight into the mechanism by which EMD affects DPSCs differentiation and proposes EMD as a promising candidate for future stem cell therapy in endodontics.
DOI: 10.1016/j.lfs.2020.117389
发表时间: 2020-03-15
期刊: LIFE SCIENCES
影响因子: 6.1
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期刊: DENTAL MATERIALS
影响因子: 5
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DOI: 10.1016/j.matbio.2015.12.001
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期刊: Matrix biology : journal of the International Society for Matrix Biology
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