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FGF4 and FGF9 have synergistic effects on odontoblast differentiation

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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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Funding

This study was supported by the Japan Society for the Promotion of Science (18H03007 and 19K19074). Genetic engineering of mice was partly supported by JST ERATO Suematsu Gas Biology (2010–2015, M.S. as the lead). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Dental Anesthesiology, Tokyo Dental College, Misaki-cho, Chiyoda-ku, Tokyo, Japan

    Tatsuki Hoshino & Tatsuya Ichinohe

  2. Department of Biochemistry, Tokyo Dental College, 2-9-18, Kanda-Misakichou, Chiyoda-ku, Tokyo, 101-0061, Japan

    Shoko Onodera & Toshifumi Azuma

  3. Department of Pediatric Dentistry, Tokyo Dental College, Misaki-cho, Chiyoda-ku, Tokyo, Japan

    Motoyoshi Kimura

  4. Department of Dental Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

    Makoto Suematsu

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  1. Tatsuki Hoshino
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  2. Shoko Onodera
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  3. Motoyoshi Kimura
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  4. Makoto Suematsu
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  5. Tatsuya Ichinohe
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  6. Toshifumi Azuma
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Correspondence to Toshifumi Azuma.

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Hoshino, T., Onodera, S., Kimura, M. et al. FGF4 and FGF9 have synergistic effects on odontoblast differentiation. Med Mol Morphol 56, 159–176 (2023). https://doi.org/10.1007/s00795-023-00351-2

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  • DOI: https://doi.org/10.1007/s00795-023-00351-2

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