Transforming Growth Factor-β Signaling Regulates Tooth Root Dentinogenesis by Cooperation With Wnt Signaling

TLDR

Proper differentiation of odontoblasts is essential for tooth root development, yet the molecular pathways orchestrating this process remain largely unclear. Loss of TGF‑β receptor type 2 in root pre‑odontoblasts induced ectopic osteogenic differentiation and abnormal root osteodentin, an effect driven by up‑regulated Wnt signaling that could be rescued by Wnt inhibition, demonstrating that TGF‑β cooperates with Wnt to regulate root odontogenic differentiation.

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; Tgfbr2 fl/fl ; Wls fl/fl mice or overexpressing the Wnt antagonist Dkk1 in Ocn-Cre; Tgfbr2 fl/fl ; ROSA26 Dkk 1 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.