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

Ran Zhang; Jingting Lin; Yang Liu; Shurong Yang; Qi He; Liang Zhu; Xiao Yang; Guan Yang

doi:10.3389/fcell.2021.687099

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

Front Cell Dev Biol. 2021 Jun 29:9:687099. doi: 10.3389/fcell.2021.687099. eCollection 2021.

Authors

Ran Zhang^{1

2}, Jingting Lin¹, Yang Liu³, Shurong Yang¹, Qi He¹, Liang Zhu¹, Xiao Yang¹, Guan Yang¹

Affiliations

¹ State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
² Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China.
³ Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China.

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 ^Dkk1 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.

Keywords: TGF-β type II receptor; Wntless; dentin; odontoblast; tooth root.