Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 9, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.687099
Keywords
TGF-beta type II receptor; Wntless; tooth root; odontoblast; dentin
Categories
Funding
- State Key Program of National Natural Science of China [31630093]
- National Natural Science Foundation of China [31871476, 31571512, 81702689]
- Beijing Nova Program [Z161100004916146]
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Proper differentiation of odontoblasts is crucial for the development of tooth roots. Disruption of TGF-beta signaling in root pre-odontoblasts leads to abnormal formation of root osteodentin and ectopic osteogenic differentiation of odontoblasts. Upregulation of Wnt signaling is observed when TGF-beta signaling is disrupted, and inhibiting Wnt signaling can reduce ectopic osteogenic differentiation and halt odontoblast differentiation.
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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