記述言語：英語   出版者・発行元：(一社)歯科基礎医学会  

記述言語：英語   出版者・発行元：Journal of Oral Biosciences  

ObjectivesTooth morphogenesis is controlled by various molecules, and the enamel knot plays a important role as a signaling center. Here, we aimed to analyze the role of AmeloD in the development of the enamel knot.MethodsThe AmeloD-stably expressing dental epithelial cell line, SF2, was established and RNA sequencing analysis was performed. The cusp morphology of AmeloD-deficient mouse molars was analyzed by micro-computed tomography. AmeloD-binding molecules were screened using the yeast two-hybrid methods.ResultsAmeloD was expressed in the enamel knot during tooth development. Proliferation was suppressed in cells overexpressing AmeloD, which was consistent with the cessation of proliferation in the enamel knot. RNA sequencing analysis revealed that the expression of proliferation-related molecules, such as Mki67, Ccnd1, and Ccnd2, decreased in AmeloD-overexpressing cells. Shh was expressed in the enamel knot, and in AmeloD-overexpressing cells, Shh promoted the expression of ameloblastin and Sox21. Furthermore, AmeloD-deficient mice had reduced intercuspal distance, mesiodistal and buccolingual diameters, and enamel hypoplasia. Odam, Selenof, Kct2, and TCF4 were identified as AmeloD-binding molecules using the yeast two-hybrid methods. AmeloD and Odam were expressed in similar regions during the earlier stages of ameloblast differentiation. To clarify how Odam regulates AmeloD, the Odam gene was transfected into AmeloD-overexpressing cells. In Odam-expressing cells, the suppression of proliferation and migration by AmeloD was inhibited.ConclusionsAmeloD promotes cell cycle arrest and activation of Shh signaling in the enamel knot, and it binds to Odam in the early stages of ameloblast differentiation, inhibiting the proliferation activity of Odam through these interactions.

DOI： 10.1016/j.job.2026.100758

Web of Science

Scopus

PubMed

記述言語：英語   出版者・発行元：(公社)日本小児歯科学会  

出版者・発行元：Pediatric Dental Journal  

Objectives: Down syndrome is caused by trisomy of chromosome 21 and shows various phenotype in organs. The patients often suffer dental anomalies such as hypodontia and enamel hypoplasia, however, the mechanism of dental anomalies associated to Down syndrome remains unclear. To clarify the details of the dental phenotype of Down syndrome, we performed RNA-sequence (RNA-seq) of dental pulp stem cells from human exfoliated deciduous tooth (SHED). Materials and methods: Three children with Down syndrome were selected as the patient group, and three healthy children were selected as the control group. Dental pulp was collected from extracted teeth during the replacement period between the ages of 5 and 8, and SHED was cultured. RT-qPCR was used to confirm whether there was a difference in the expression level of the gene on chromosome 21. MTT assay and colony formation assay was performed to examine cell proliferation ability. RNA-seq was performed to comprehensively analyze the gene expression difference between control group and Down syndrome group. Results: SHED of control group and Down syndrome group showed no significant difference in cell shape and proliferation activity, while, the expression of COL6A1 was around 1.5-fold change upregulated in Down syndrome group, suggesting that the gene of chromosome 21 became trisomy. RNA-seq analyses revealed that the genes related to organ morphogenesis were upregulated. Furthermore, several genes important for tooth development was raised as significantly upregulated genes. Conclusion: Genetic analysis using SHED was considered a useful tool for elucidating the mechanisms of dental anomalies in Down syndrome.

DOI： 10.1016/j.pdj.2025.100360

Web of Science

Scopus

記述言語：英語   出版者・発行元：Journal of Cellular Physiology  

Keratins are typical intermediate filament proteins of the epithelium that exhibit highly specific expression patterns related to the epithelial type and stage of cellular differentiation. They are important for cytoplasmic stability and epithelial integrity and are involved in various intracellular signaling pathways. Several keratins are associated with enamel formation. However, information on their expression patterns during tooth development remains lacking. In this study, we analyzed the spatiotemporal expression of keratin family members during tooth development using single-cell RNA-sequencing (scRNA-seq) and microarray analysis. scRNA-seq datasets from postnatal Day 1 mouse molars revealed that several keratins are highly expressed in the dental epithelium, indicating the involvement of keratin family members in cellular functions. Among various keratins, keratin 5 (Krt5), keratin 14 (Krt14), and keratin 17 (Krt17) are highly expressed in the tooth germ; KRT17 is specifically expressed in the stratum intermedium (SI) and stellate reticulum (SR). Depletion of Krt17 did not affect cell proliferation in the dental epithelial cell line SF2 but suppressed their differentiation ability. These results suggest that Krt17 is essential for SI cell differentiation. Furthermore, scRNA-seq results indicated that Krt5, Krt14, and Krt17 exhibited distinct expression patterns in ameloblast, SI, and SR cells. Our findings contribute to the elucidation of novel mechanisms underlying tooth development.

DOI： 10.1002/jcp.31387

Web of Science

Scopus

PubMed

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   出版者・発行元：(株)ヒョーロン・パブリッシャーズ