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

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; Tgfbr2fl/fl; Wlsfl/fl mice or overexpressing the Wnt antagonist Dkk1 in Ocn-Cre; Tgfbr2fl/fl; ROSA26Dkk1 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.

The Critical Role of MMP13 in Regulating Tooth Development and Reactionary Dentinogenesis Repair Through the Wnt Signaling Pathway

“…Of these, the Wnt signaling pathway ( Figure 7 ) was of particular interest due to its critical role in tooth development and odontoblast function ( Lohi et al, 2010 ), with Axin2 and Wnt10a significantly downregulated in MMP13KO samples, both of which have previously been highlighted to be reduced in the odontoblasts of malformed crowns in Wnt-less mice ( Bae et al, 2015 ). Wnt10a expression has been shown to induce DSP expression and odontoblast differentiation ( Yamashiro et al, 2007 ), while Axin2 expression in odontoblasts has been shown to enhance reparative dentinogenesis ( Babb et al, 2017 ) and root thickness ( Zhang et al, 2021 ) and has implicated Wnt/β-catenin signaling in odontoblast development and maturation ( Lohi et al, 2010 ; Babb et al, 2017 ). Axin2 is a direct target of canonical Wnt signaling ( Kim and Simmer 2007 ) and is seen in a restricted pattern during mouse embryogenesis and organogenesis with reports suggesting that Axin2 participates in a negative feedback loop that limits the duration of a Wnt-initiated signal ( Jho et al, 2002 ).…”

The Effects of Transforming Growth Factor-β1 on the Differentiation of Cell Organoids Composed of Gingiva-Derived Stem Cells

“…Animal models with the deletion of transforming growth factor- β receptor type 2 in bone-producing mesenchyme led to an alteration in osteoblast organization [ 48 ]. Similarly, the deletion of transforming growth factor- β receptor type 2 in odontoblastic precursor cells resulted in the abnormal development of osteodentin [ 49 ].…”

Genetic Diversity and Runs of homozygosity analysis of Hetian Sheep Populations Revealed by Illumina OvineSNP50 BeadChip

“…In addition, 16 KEGG _ PATHWAY was enriched to 96 genes, and oas01100 (Metabolic pathways) were mainly enriched to 48 speci c genes. Genes WNT6, WNT10A, LEF1 and TCF7L1 were enriched in oas04310 (Wnt signaling pathway), oas04916 (Melanogenesis), oas05217 (Basal cell carcinoma pathway).The expression of WNT6 and WNT10A can stimulate the formation and differentiation of osteoblasts and play an important role in maintaining bone homeostasis [31] .Meanwhile, bone differentiation can promote the formation of the Generation of Osteocalcin and regulate tooth formation [52] . On the other hand, WNT signaling promotes the proliferation of melanocyte stem cells and drives their differentiation to produce pigment [53] .…”