WNT10A variants in relation to nonsyndromic hypodontia in eastern Slovak population

Grejtáková, Daniela; Gabrikova-Dojcakova, D.; Boroňová, Iveta; Kyjovska, L.; Hubcejova, J.; Fecenkova, M.; Zigová, Michaela; Priganc, Mariana; Bernasovská, Jarmila

doi:10.1007/s12041-018-1011-z

Cited by 11 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The C107* variant, predicted to result in a premature stop codon, was still able to retain signaling activity, indicating that compensating mechanisms may exist to rescue the variant-induced suspected loss of function. Collectively, these findings are in general agreement with our in silico predictions and previous reports (Dinckan et al 2018; Grejtakova et al 2018). The variants R113C, V145M, R171C, and R379C also appear to retain some wild-type–like activity able to sustain protein function.…”

Section: Discussionsupporting

confidence: 94%

Functional Effects of WNT10A Rare Variants Associated with Tooth Agenesis

et al. 2020

View full text Add to dashboard Cite

Mutations in WNT10A have frequently been reported as etiologic for tooth agenesis (TA). However, the effects of WNT10A variation on gene/protein function and contribution to TA phenotypes remain poorly understood. Here, we performed bioinformatic and functional characterization analysis of WNT10A variants. In silico prediction of variant function was performed with VIPUR for all WNT10A missense variants reported in the Exome Aggregation Consortium database. Functional characterization experiments were then performed for selected WNT10A variants previously associated with TA. Expression vectors for wild-type and mutant WNT10A were made and transfected into stem cells from human exfoliated deciduous teeth (SHED) for evaluation of gene/protein function, WNT signaling activity, and effects on expression of relevant genes. While 75% of WNT10A variants were predicted neutral, most of the TA-associated variants received deleterious scores by potentially destabilizing or preventing the disulfide bond formation required for proper protein function. WNT signaling was significantly decreased with 8 of 13 variants tested, whereas wild-type–like activity was retained with 4 of 13 variants. WNT10A-mutant cells (T357I, R360C, and R379C mutants) showed reduced or impaired binding affinity to FZD5, suggesting a potential mechanism for the decreased WNT signaling. Mutant cells also had decreased WNT10A protein expression in comparison to wild-type cells. mRNA expression of PAX9, MSX1, AXIN2, and RUNX2 (known tooth development genes) was perturbed in mutant cells and quite significantly for PAX9 and RUNX2. Transcriptome analysis of wild-type and T357I-mutant cells identified 36 differentially expressed genes (26 downregulated, 10 upregulated) involved in skeletal system development and morphogenesis and pattern specification. WNT10A variants deemed pathogenic for TA likely affect protein folding and/or stabilization, leading to decreased WNT signaling and concomitant dysregulated expression of relevant genes. These findings may allow for improved interpretation of TA phenotypes upon clinical diagnosis while providing important insights toward the development of future tooth replacement therapies.

show abstract

Section: Discussionsupporting

confidence: 94%

Functional Effects of WNT10A Rare Variants Associated with Tooth Agenesis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…When the tooth is damaged due to caries, mechanical wear and trauma, the in ammatory reaction will stimulate the pulp stem cells to perform the repair function. The study using abrasion and cutting methods aims to simulate the dental pulp exposure caused by caries, iatrogenic pulp perforation and trauma directly caused by tooth fracture in clinical practice and to analyze the situation of dental repair after injury under different circumstances more comprehensively [24][25][26][27][28][29] . Early studies have shown that when the dental pulp is damaged severely, the dental pulp cells migrate from the central area of the dental pulp to the marginal area of the dental pulp and differentiate into odontoblasts, which replace the necrotic odontoblasts to produce restorative dentin [30][31][32] .…”

Section: Discussionmentioning

confidence: 99%

Effect of Wnt/β-catenin signaling pathway on repair and regeneration after dentin-pulp injury

Xing

et al. 2023

Preprint

View full text Add to dashboard Cite

The Wnt/β-catenin signaling pathway performs multiple essential functions during tooth development. Several Wnt/β-catenin signaling pathway components are expressed in the dental epithelium and mesenchyme during tooth development in humans and mice. Functional studies and experimental analyses in relevant animal models have confirmed the regulatory role of the Wnt/β-catenin signaling pathway on developing tooth formation and adult dental homeostasis. In this study, we used the adult mouse incisor as a model to explore the effect of the Wnt/β-catenin signaling pathway on the repair and regeneration of dental pulp stem cells after injury. We established the dentin-pulp injury models successfully in two different ways and observed an obvious injury in the proximal region of the adult mouse incisor in each group. Faster repair and regeneration were detected after Wnt/β-catenin signaling activation and vice versa, indicating that Wnt/β-catenin signaling is required for cell proliferation and odontoblast differentiation. The same results were further verified by culturing mouse DPSCs in vitro. In our experiments, we found that Wnt10a also showed significant expression when the Wnt/β-catenin signaling pathway was activated and further demonstrated that Wnt10a-mediated Wnt/β-catenin signaling plays a positive regulatory role to regulate DPSCs proliferation and odontoblast differentiation and promoting the repair process of incisor injury. This study highlights the crucial role of the Wnt/β-catenin signaling pathway in the tooth injury and repair and shed new lights on the discovery of novel molecular mechanisms associated with tooth regeneration.

show abstract

“…Analysis of the gene database showed that most of the mutations (91.9%) in individuals with non‐syndromic dental hypoplasia were related to mutations in Wnts or its related genes (Yu et al, 2019). Gene mutations of Wnt10a were associated with dental hypoplasia, which was indicated by two genetic analyses of patients with dental hypoplasia in Turkey and Slovakia (Du et al, 2018; Grejtakova et al, 2018). A genetic study of Pakistani patients found a new case of Wnt10a gene mutation (c.311G>A; p. Arg104His) causing dental dysplasia (Parveen et al, 2019).…”

Section: Wnt and Other Diseasesmentioning

confidence: 97%

Wnt signalling in oral and maxillofacial diseases

Zhang

Pan

Chen

et al. 2021

Cell Biology International

View full text Add to dashboard Cite

Wnts include more than 19 types of secreted glycoproteins that are involved in a wide range of pathological processes in oral and maxillofacial diseases. The transmission of Wnt signalling from the extracellular matrix into the nucleus includes canonical pathways and noncanonical pathways, which play an important role in tooth development, alveolar bone regeneration, and related diseases. In recent years, with the in‐depth study of Wnt signalling in oral and maxillofacial‐related diseases, many new conclusions and perspectives have been reached, and there are also some controversies. This article aims to summarise the roles of Wnt signalling in various oral diseases, including periodontitis, dental pulp disease, jaw disease, cleft palate, and abnormal tooth development, to provide researchers with a better and more comprehensive understanding of Wnts in oral and maxillofacial diseases.

show abstract

WNT10A variants in relation to nonsyndromic hypodontia in eastern Slovak population

Cited by 11 publications

References 32 publications

Functional Effects of WNT10A Rare Variants Associated with Tooth Agenesis

Functional Effects of WNT10A Rare Variants Associated with Tooth Agenesis

Effect of Wnt/β-catenin signaling pathway on repair and regeneration after dentin-pulp injury

Wnt signalling in oral and maxillofacial diseases

Contact Info

Product

Resources

About