Abstract
Fibroblast growth factor 8 (FGF8) is known to be a potent stimulator of canonical Wnt/β-catenin activity, an essential factor for tooth development. In this study, we analyzed the effects of co-administration of FGF8 and a CHIR99021 (GSK3β inhibitor) on differentiation of dental mesenchymal cells into odontoblasts. Utilizing Cre-mediated EGFP reporter mice, dentin matrix protein 1 (Dmp1) expression was examined in mouse neonatal molar tooth germs. At birth, expression of Dmp1-EGFP was not found in mesenchymal cells but rather epithelial cells, after which Dmp1-positive cells gradually emerged in the mesenchymal area along with disappearance in the epithelial area. Primary cultured mesenchymal cells from neonatal tooth germ specimens showed loss of Dmp1-EGFP positive signals, whereas addition of Wnt3a or the CHIR99021 significantly regained Dmp1 positivity within approximately 2 weeks. Other odontoblast markers such as dentin sialophosphoprotein (Dspp) could not be clearly detected. Concurrent stimulation of primary cultured mesenchymal cells with the CHIR99021 and FGF8 resulted in significant upregulation of odonto/osteoblast proteins. Furthermore, increased expression levels of runt-related transcription factor 2 (Runx2), osterix, and osteocalcin were also observed. The present findings indicate that coordinated action of canonical Wnt/β-catenin and FGF8 signals is essential for odontoblast differentiation of tooth germs in mice.
Highlights
Tooth development is initiated by thickening of oral epithelium and adjacent cranial neural crest (CNC) derivedmesenchyme, after which this epithelial-mesenchymal complex becomes invaginated into the underlying CNC to form a tooth bud
The present results show that interaction between the Wnt canonical pathway and Fibroblast growth factor 8 (FGF8) is important for odontoblast differentiation, providing new evidence for elucidation of the mechanism of tooth development
There was nearly no EGFP expression detected in the dental mesenchyme area in newborn dentin matrix protein 1 (Dmp1)-EGFP mice, while that was noted in ameloblast areas (Fig. 1a–c)
Summary
Tooth development is initiated by thickening of oral epithelium and adjacent cranial neural crest (CNC) derivedmesenchyme, after which this epithelial-mesenchymal complex becomes invaginated into the underlying CNC to form a tooth bud. The molecular regulation of early tooth morphogenesis leading to tooth bud formation has been extensively studied. A large body of work shows that the network controlling tooth development includes major signaling pathways, such as those of transforming growth factor β (TGFβ), BMP, FGF, Wnt, and SHH, indicating recurrent functions at various stages [3, 4]. The precise molecular network controlling the late stages of tooth development including odontoblast differentiation is very complex and yet to be determined [5], and there is a need to provide more comprehensive understanding of odontoblast development
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
