TY - JOUR
T1 - FGF4 and FGF9 have synergistic effects on odontoblast differentiation
AU - Hoshino, Tatsuki
AU - Onodera, Shoko
AU - Kimura, Motoyoshi
AU - Suematsu, Makoto
AU - Ichinohe, Tatsuya
AU - Azuma, Toshifumi
N1 - Funding Information:
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.
Publisher Copyright:
© 2023, The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Dmp1
KW - Enamel knot
KW - FGF4
KW - FGF9
KW - Mesenchymal cells
KW - Odontoblast
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U2 - 10.1007/s00795-023-00351-2
DO - 10.1007/s00795-023-00351-2
M3 - Article
AN - SCOPUS:85151487732
SN - 1860-1480
JO - Medical Molecular Morphology
JF - Medical Molecular Morphology
ER -