Constitutive activation of β-catenin in odontoblasts induces aberrant pulp calcification in mouse incisors

Deng, Shijian; Fan, Linlin; Wang, Yunfei; Zhang, Qi

doi:10.1007/s10735-021-09965-1

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…In addition, a previous study has shown that activating the Wnt signal by βcatenin resulted in excessive predentin production by odontoblasts (Kim et al, 2011), which supports our finding. Importantly, constitutively activated β-catenin in odontoblasts resulted in disorganization and depolarization of incisor odontoblasts (Deng et al, 2021), which was similar to the results of Rainbow mice. Also, we believe that the loss of the odontoblast process may inhibit the generation of dentinal tubules, as previously reported (Chang et al, 2019).…”

Section: Discussionsupporting

confidence: 78%

Ptip is essential for tooth development via regulating Wnt pathway

Liang

Wang

et al. 2023

Oral Diseases

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ObjectiveEpigenetic regulation plays important role in stem cell maintenance. Ptip was identified as epigenetic regulator, but the role in dental progenitor cells remains unclear.Subjects and MethodsDental mesenchymal progenitor cells were targeted by Sp7‐icre and visualized in mTmG; Sp7‐icre mice. The Ptipf/f; Sp7‐icre mice were generated and the phenotype of incisors and molars were shown by micro‐computerized tomography, scanning electron microscope, hematoxylin & eosin staining, and immunofluorescence. Dental mesenchymal progenitor cells were sorted by fluorescence‐activated cell sorting from lower incisors and RNA sequencing was performed.ResultsThe Sp7‐icre targets dental mesenchymal progenitor cells in incisors and molars. The Ptipf/f; Sp7‐icre mice showed spontaneous fractures in the cusp of upper incisors and lower incisors at 3 weeks (w), compensative overgrowth of lower incisors at 1 month (M), and overgrowth extended to the outside at 2 M. The molars showed shortened roots. The functions of odontoblasts and dental mesenchymal progenitor cells were impaired. Mechanically, loss of Ptip activates the Wnt pathway and upregulates the expression of Wls in dental mesenchymal progenitor cells. Also, the regenerative ability of lower incisors was significantly impaired.ConclusionWe first demonstrated that Ptip was crucial for tooth development via regulating Wnt signaling.

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Section: Discussionsupporting

confidence: 78%

Ptip is essential for tooth development via regulating Wnt pathway

Liang

Wang

et al. 2023

Oral Diseases

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“…According to the report, osteodentin was formed in the molar pulps after deleted Bmp2 using Osx - Cre [ 17 ]. Knockdown β-catenin using Col1 - Cre ERT2 resulted in aberrant pulp calcification in mouse incisors [ 30 ]. The above findings suggested that osteodentin in the incisors of Stat3 CKO mice was most likely to be caused by Stat3 -deficiency.…”

Section: Discussionmentioning

confidence: 99%

Loss of Stat3 in Osterix+ cells impairs dental hard tissues development

Chan

Feng

et al. 2023

Cell Biosci

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Background Mutations in the signal transducers and activators of transcription 3 (STAT3) gene result in hyper-IgE syndrome(HIES), a rare immunodeficiency that causes abnormalities in immune system, bones and teeth. However, the role of Stat3 in development of dental hard tissues was yet to investigate. Methods In this study, a transgenic mouse of conditional knockout of Stat3 in dental mesenchymal cells (Osx-Cre; Stat3fl/fl, Stat3 CKO) was made. The differences of postnatal tooth development between control and Stat3 CKO mice were compared by histology, µCT and scanning electron microscopy. Result Compared with the control, Stat3 CKO mice were presented with remarkable abnormal tooth phenotypes characterized by short root and thin dentin in molars and incisors. The enamel defects were also found on mandibular incisors. showed that Ki67-positive cells significantly decreased in dental mesenchymal of Stat3 CKO mice. In addition, β-catenin signaling was reduced in Hertwig's epithelial root sheath (HERS) and odontoblasts of Stat3 CKO mice. Conclusions Our results suggested that Stat3 played an important role in dental hard tissues development, and Stat3 may regulate dentin and tooth root development through the β-catenin signaling pathway.

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“…Previous studies have revealed the indispensable role of Wnt/ β-catenin signaling in tooth development (Deng et al, 2021;Kim et al, 2011). However, it was more reasonable and convincing that we explored the role of Wnt signaling only in those Axin2-expressing Wnt-responsive cells, as Axin2 is expressed in cell populations responsive to Wnt/β-catenin signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence demonstrated that the level of β‐catenin has a great impact on tooth morphogenesis (Bae et al, 2013; Kim et al, 2013). The failure of degradation of β‐catenin constantly activates Wnt signaling, which is related to aberrant pulp calcification and dental ankylosis in mice (Deng et al, 2021; Wu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Activation of Wnt signaling in Axin2⁺ cells leads to osteodentin formation and cementum overgrowth

Shi

Xie

et al. 2022

Oral Diseases

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ObjectivesIn this study, we used the mouse incisor model to investigate the regulatory mechanisms of Wnt/β‐catenin signaling on Axin2+ cells in tooth development.Materials and MethodsAxin2lacZ/+ reporter mice were used to define the expression pattern of Axin2 in mouse incisors. We traced the fate of Axin2+ cells from postnatal Day 21 (P21) to P56 using Axin2CreERT2/+ and R26RtdTomato/+ reporter mice. For constitutive activation of Wnt signaling, Axin2CreERT2/+, β‐cateninflox(Ex3)/+, and R26RtdTomato/+ (CA‐β‐cat) mice were generated to investigate the gain of function (GOF) of β‐catenin in mouse incisor growth.ResultsThe X‐gal staining of Axin2lacZ/+ reporter mice and lineage tracing showed that Axin2 was widely expressed in dental mesenchyme of mouse incisors, and Axin2+ cells were essential cell sources for odontoblasts, pulp cells, and periodontal ligament cells. The constitutive activation of Wnt signaling in Axin2+ cells resulted in the formation of osteodentin featured with increased DMP1 and dispersed DSP expression and overgrowth of cementum.ConclusionWnt signaling plays a key role in the differentiation and maturation of Axin2+ cells in mouse incisors.

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Constitutive activation of β-catenin in odontoblasts induces aberrant pulp calcification in mouse incisors

Cited by 4 publications

References 38 publications

Ptip is essential for tooth development via regulating Wnt pathway

Ptip is essential for tooth development via regulating Wnt pathway

Loss of Stat3 in Osterix+ cells impairs dental hard tissues development

Activation of Wnt signaling in Axin2⁺ cells leads to osteodentin formation and cementum overgrowth

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Constitutive activation of β-catenin in odontoblasts induces aberrant pulp calcification in mouse incisors

Cited by 4 publications

References 38 publications

Ptip is essential for tooth development via regulating Wnt pathway

Ptip is essential for tooth development via regulating Wnt pathway

Loss of Stat3 in Osterix+ cells impairs dental hard tissues development

Activation of Wnt signaling in Axin2+ cells leads to osteodentin formation and cementum overgrowth

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Activation of Wnt signaling in Axin2⁺ cells leads to osteodentin formation and cementum overgrowth