Effect of attenuation of fibroblast growth factor receptor 2b signaling on odontoblast differentiation and dentin formation.

Abstract

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 2weeks 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.