FGF4 and FGF9 have synergistic effects on odontoblast differentiation.

IF 1.2 4区医学 Q3 PATHOLOGY Medical Molecular Morphology Pub Date : 2023-09-01 Epub Date: 2023-04-03 DOI:10.1007/s00795-023-00351-2

Tatsuki Hoshino, Shoko Onodera, Motoyoshi Kimura, Makoto Suematsu, Tatsuya Ichinohe, Toshifumi Azuma

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Abstract

The purpose of this study was to investigate whether fibroblast growth factor 4 (FGF4) and FGF9 are active in dentin differentiation. Dentin matrix protein 1 (Dmp1) -2A-Cre transgenic mice, which express the Cre-recombinase in Dmp1-expressing cells, were crossed with CAG-tdTomato mice as reporter mouse. The cell proliferation and tdTomato expressions were observed. The mesenchymal cell separated from neonatal molar tooth germ were cultured with or without FGF4, FGF9, and with or without their inhibitors ferulic acid and infigratinib (BGJ398) for 21 days. Their phenotypes were evaluated by cell count, flow cytometry, and real-time PCR. Immunohistochemistry for FGFR1, 2, and 3 expression and the expression of DMP1 were performed. FGF4 treatment of mesenchymal cells obtained promoted the expression of all odontoblast markers. FGF9 failed to enhance dentin sialophosphoprotein (Dspp) expression levels. Runt-related transcription factor 2 (Runx2) was upregulated until day 14 but was downregulated on day 21. Compared to Dmp1-negative cells, Dmp1-positive cells expressed higher levels of all odontoblast markers, except for Runx2. Simultaneous treatment with FGF4 and FGF9 had a synergistic effect on odontoblast differentiation, suggesting that they may play a role in odontoblast maturation.

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FGF4和FGF9对成牙本质细胞分化具有协同作用。

本研究的目的是研究成纤维细胞生长因子4（FGF4）和FGF9在牙本质分化中是否具有活性。将在表达Dmp1的细胞中表达Cre重组酶的Dentin基质蛋白1（Dmp1）-2A-Cre转基因小鼠与CAG-tdTtomato小鼠杂交作为报告小鼠。观察细胞增殖和tdTomato的表达。从新生儿磨牙胚中分离的间充质细胞在有或没有FGF4、FGF9以及有或没有它们的抑制剂阿魏酸和异格拉替尼（BGJ398）的情况下培养21天。通过细胞计数、流式细胞术和实时聚合酶链式反应评估其表型。免疫组化检测FGFR1、2和3的表达以及DMP1的表达。所获得的间充质细胞的FGF4处理促进了所有成牙本质细胞标志物的表达。FGF9不能提高牙本质唾液磷蛋白（Dspp）的表达水平。Runt相关转录因子2（Runx2）上调至第14天，但在第21天下调。与Dmp1阴性细胞相比，除Runx2外，Dmp1阳性细胞表达更高水平的所有成牙本质细胞标志物。FGF4和FGF9同时治疗对成牙本质细胞分化具有协同作用，表明它们可能在成牙本质成熟中发挥作用。

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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.