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Comprehensive Analysis of Transcription Factors Involved in Odontoblast Differentiation Mechanism

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Journal Med Mol Morphol
Publisher Springer
Date 2024 Jul 10
PMID 38987402
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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.

References
1.
Vos T, Flaxman A, Naghavi M, Lozano R, Michaud C, Ezzati M . Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012; 380(9859):2163-96. PMC: 6350784. DOI: 10.1016/S0140-6736(12)61729-2. View

2.
Sedgley C, Messer H . Are endodontically treated teeth more brittle?. J Endod. 1992; 18(7):332-5. DOI: 10.1016/S0099-2399(06)80483-8. View

3.
Gronthos S, Mankani M, Brahim J, Robey P, Shi S . Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000; 97(25):13625-30. PMC: 17626. DOI: 10.1073/pnas.240309797. View

4.
Batouli S, Miura M, Brahim J, Tsutsui T, Fisher L, Gronthos S . Comparison of stem-cell-mediated osteogenesis and dentinogenesis. J Dent Res. 2003; 82(12):976-81. DOI: 10.1177/154405910308201208. View

5.
Nakao K, Morita R, Saji Y, Ishida K, Tomita Y, Ogawa M . The development of a bioengineered organ germ method. Nat Methods. 2007; 4(3):227-30. DOI: 10.1038/nmeth1012. View