AUTHOR=Zhang Ran , Lin Jingting , Liu Yang , Yang Shurong , He Qi , Zhu Liang , Yang Xiao , Yang Guan 

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.687099

DOI=10.3389/fcell.2021.687099

ISSN=2296-634X

ABSTRACT=<p>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 <italic>transforming growth factor-</italic>β <italic>receptor type 2</italic> (<italic>Tgfbr2</italic>) 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 <italic>Wnt6</italic>, <italic>Wnt10a</italic>, <italic>Tcf-1</italic>, and <italic>Axin2</italic> expression. Interestingly, inhibiting Wnt signaling by deleting <italic>Wntless</italic> (<italic>wls</italic>) in <italic>Osteocalcin</italic> (<italic>Ocn</italic>)<italic>-Cre; Tgfbr2<sup><italic>fl/fl</italic></sup>; Wls<sup><italic>fl/fl</italic></sup></italic> mice or overexpressing the Wnt antagonist <italic>Dkk1</italic> in <italic>Ocn-Cre; Tgfbr2<sup><italic>fl/fl</italic></sup>; ROSA26<sup><italic>Dkk</italic>1</sup></italic> 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.</p>