Comprehensive analysis of transcription factors involved in odontoblast differentiation mechanism.

IF 1.2 4区医学 Q3 PATHOLOGY

Medical Molecular Morphology Pub Date : 2024-12-01 Epub Date: 2024-07-11 DOI:10.1007/s00795-024-00389-w

Haruka Nakazato, Shoko Onodera, Natsuko Aida, Masahiro Furusawa, Toshifumi Azuma

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Abstract

Primary cultured odontoblasts rapidly lose their tissue-specific phenotype. To identify transcription factors (TF) that are important for the maintenance of the odontoblast phenotype, primary cultures of C57BL/6 J mouse dental mesenchymal cells (DMC) were isolated, and expression of TF and odontoblast marker genes in cells immediately after isolation and 2 days after culture were comprehensively evaluated and compared using RNA-sequencing (RNA-seq). The expression of odontoblast markers in mouse dental mesenchymal cells decreased rapidly after isolation. In addition, the expression of Hedgehog-related, Notch-related, and immediate- early gene (IEG)-related transcription factors significantly decreased. Forced expression of these genes in lentiviral vectors, together with fibroblast growth factor 4 (FGF4), fibroblast growth factor 9 (FGF9), and the Wnt pathway activator CHIR99021, significantly induced the expression of odontogenic marker genes. These results indicate, for the first time, that Notch signaling and early genes may be important for maintaining odontoblast cultures. Furthermore, simultaneous stimulation of FGF, Wnt, Hedgehog, Notch pathways, and IEG transcription factors cooperatively promoted the maintenance of the odontoblast phenotype. These results suggest that the Hedgehog and Notch signaling pathways may play an important role in maintaining odontoblast phenotypes, in addition to FGF and Wnt signaling.

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全面分析参与骨母细胞分化机制的转录因子

原代培养的牙本质细胞会迅速失去其组织特异性表型。为了确定对维持牙突母细胞表型起重要作用的转录因子（TF），我们分离了 C57BL/6 J 小鼠牙间质细胞（DMC）的原代培养物，并使用 RNA 序列（RNA-seq）对分离后立即和培养 2 天后细胞中 TF 和牙突母细胞标记基因的表达进行了全面评估和比较。结果表明，小鼠牙间质细胞中骨母细胞标记基因的表达在分离后迅速下降。此外，Hedgehog 相关基因、Notch 相关基因和即时早期基因 (IEG) 相关转录因子的表达也显著下降。在慢病毒载体中强制表达这些基因以及成纤维细胞生长因子 4（FGF4）、成纤维细胞生长因子 9（FGF9）和 Wnt 通路激活剂 CHIR99021，可显著诱导牙源性标记基因的表达。这些结果首次表明，Notch 信号和早期基因可能对维持牙本质细胞培养非常重要。此外，同时刺激 FGF、Wnt、Hedgehog、Notch 通路和 IEG 转录因子可协同促进牙本质细胞表型的维持。这些结果表明，除 FGF 和 Wnt 信号外，Hedgehog 和 Notch 信号通路可能在维持畸骨母细胞表型方面发挥重要作用。

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来源期刊

Medical Molecular Morphology 医学-病理学

CiteScore

2.90

自引率

5.60%

发文量

审稿时长

>12 weeks

期刊介绍： Medical Molecular Morphology is an international forum for researchers in both basic and clinical medicine to present and discuss new research on the structural mechanisms and the processes of health and disease at the molecular level. The structures of molecules, organelles, cells, tissues, and organs determine their normal function. Disease is thus best understood in terms of structural changes in these different levels of biological organization, especially in molecules and molecular interactions as well as the cellular localization of chemical components. Medical Molecular Morphology welcomes articles on basic or clinical research in the fields of cell biology, molecular biology, and medical, veterinary, and dental sciences using techniques for structural research such as electron microscopy, confocal laser scanning microscopy, enzyme histochemistry, immunohistochemistry, radioautography, X-ray microanalysis, and in situ hybridization. Manuscripts submitted for publication must contain a statement to the effect that all human studies have been reviewed by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in an appropriate version of the 1964 Declaration of Helsinki. It should also be stated clearly in the text that all persons gave their informed consent prior to their inclusion in the study. Details that might disclose the identity of the subjects under study should be omitted.