Effect of attenuation of fibroblast growth factor receptor 2b signaling on odontoblast differentiation and dentin formation
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Attenuation of fibroblast growth factor receptor (FGFR) 2b signaling suppresses the differentiation of oral epithelial stem cells to ameloblasts, their survival and viability remaining unaffected; however, its effect on dentin formation is unknown. This study aimed to clarify the effect of attenuation of FGFR2b signaling on odontoblast differentiation and dentin formation. Initially, we used a murine rtTA transactivator/tetracycline promoter system for inducible and reversible attenuation of FGFR2b signaling in adult mice. Experimental animals overexpressed soluble FGFR2b (sFGFR2b), and wild-type controls were selected from the same litter (WT group). Histological analysis of CMV mice confirmed the obliteration of the enamel and ameloblast layer, and micro CT analysis revealed a significant increase in dentin thickness in CMV mice rather than in WT mice (P < 0.05). On analyzing the expression of dentin-related differentiation factors, DSPP, nestin, and OCN were upregulated in CMV mice compared to WT mice after 2 weeks of attenuation of FGFR2b signaling. Thereafter, on overexpressing sFGFR2b in dental pulp stem cells, RUNX2 and ALP were upregulated; however, DSPP, nestin, and OCN were downregulated in CMV mice compared to WT mice. The present results show that attenuation of FGFR2b signaling in the oral epithelium specifically induced odontoblast differentiation and promotes early-stage dentin calcification in dental pulp tissue.
KeywordsDentin calcification Odontoblast differentiation Fibroblast growth factor receptor 2b Attenuation Dental pulp tissue
Advice and comments given by Dr. Ichiro Takahashi, Department of Mucosal Immunology, Hiroshima University and Dr. Naoya Kakimoto, Department of Oral and Maxillofacial Radiology, Hiroshima University, have been a great help in this report. The authors thank Dr. Shinji Hiyama, Hiroshima University, and Dr. Shigeki Suzuki, Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, for providing technical support.
This study was supported by a Grant-in-Aid for Scientific Research from the National Institute of Biomedical Innovation in Japan (Project ID 16 K115920).
Compliance with ethical standards
This study was approved by the Hiroshima University Animal Experiment Facility (Hiroshima University Animal Experiment Approval No. A14-144, Genetically Modified Organism Experiment Approval No. 26-220).
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