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

被引：15
作者：
Zhang, Ran [1 ,2 ]
Lin, Jingting [1 ]
Liu, Yang [3 ]
Yang, Shurong [1 ]
He, Qi [1 ]
Zhu, Liang [1 ]
Yang, Xiao [1 ]
Yang, Guan [1 ]
机构：
[1] Beijing Inst Lifeom, Natl Ctr Prot Sci Beijing, State Key Lab Prote, Beijing Proteome Res Ctr, Beijing, Peoples R China
[2] Peking Univ, Sch & Hosp Stomatol, Dept Oral Pathol, Beijing, Peoples R China
[3] Peking Univ, Dept Prosthodont, Sch & Hosp Stomatol,Boling Key Lab Digital Stomat, Natl Clin Res Ctr Oral Dis,Natl Engn Lab Digital, Beijing, Peoples R China
来源：
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷
基金：
中国国家自然科学基金;
关键词：
TGF-beta type II receptor; Wntless; tooth root; odontoblast; dentin; TGF-BETA; CELL FATE; ODONTOBLAST DIFFERENTIATION; CATENIN; DISRUPTION; EXPRESSION; REQUIREMENT; PATHWAYS; PROMOTES; OSTERIX;
D O I：
10.3389/fcell.2021.687099
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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-beta 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-beta 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-beta signaling acts with Wnt signaling to regulate root odontogenic differentiation.
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页数：11
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