Abstract

Proper differentiation of odontoblasts is crucial for the development of tooth roots. Previous studies have reported the osteogenic/odontogenic potential of pre-odontoblasts during root odontoblast differentiation. However, the underlying molecular pathway that orchestrates these processes remains largely unclear. In this study, ablation of transforming growth factor-β receptor type 2 (Tgfbr2) in root pre-odontoblasts resulted in abnormal formation of root osteodentin, which was associated with ectopic osteogenic differentiation of root odontoblasts. Disrupting TGF-β signaling caused upregulation of Wnt signaling characterized by increased Wnt6, Wnt10a, Tcf-1, and Axin2 expression. Interestingly, inhibiting Wnt signaling by deleting Wntless (wls) in Osteocalcin (Ocn)-Cre; Tgfbr2fl/fl; Wlsfl/fl mice or overexpressing the Wnt antagonist Dkk1 in Ocn-Cre; Tgfbr2fl/fl; ROSA26Dkk1 mice decreased ectopic osteogenic differentiation and arrested odontoblast differentiation. Our results suggest that TGF-β signaling acts with Wnt signaling to regulate root odontogenic differentiation.

Highlights

  • The mechanism of crown dentinogenesis has been well studied; knowledge about root dentinogenesis is only emerging (Park et al, 2007; Zhang et al, 2015; Li et al, 2017)

  • To test the role of Transforming growth factor-β (TGF-β) signaling in root dentinogenesis during the development of tooth roots, we employed the OcnCre strain to disrupt TGF-β signaling in Ocn-Cre; Tgfbr2fl/fl mice

  • During tooth root development, p-Smad2/3 is strongly expressed in dental papilla, moderately expressed in odontoblasts, indicating a stage-specific role of TGF-β signaling in root odontoblast differentiation (Li and Pan, 2018)

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Summary

Introduction

The mechanism of crown dentinogenesis has been well studied; knowledge about root dentinogenesis is only emerging (Park et al, 2007; Zhang et al, 2015; Li et al, 2017). The cranial neural crest derived mesenchyme condenses around and continuously interacts with Hertwig’s epithelial root sheath (Huang et al, 2009). The apical papilla mesenchyme undergoes differentiation into pre-odontoblasts, which terminally differentiate to become odontoblasts (Ruch et al, 1995). This process is marked by the expression of several genes that encode collagenous and non-collagenous proteins that are found in osteoblasts and the bone matrix (Gaikwad et al, 2001). The overlapping pattern of gene expression suggests the divergence of a common pool of progenitor cells for odontoblasts and osteoblasts. The molecular mechanism that controls the osteo/odontogenic differentiation of root dental mesenchyme remains largely unknown

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