Overactivation of the NF‐κB pathway impairs molar enamel formation
Open accessAbstract
Objective: Hypohidrotic ectodermal dysplasia (HED) is a hereditary disorder characterized by abnormal structures and functions of the ectoderm‐derived organs, including teeth. HED patients exhibit a variety of dental symptoms, such as hypodontia. Although disruption of the EDA/EDAR/EDARADD/NF‐κB pathway is known to be responsible for HED, it remains unclear whether this pathway is involved in the process of enamel formation. Experimental subjects and methods: To address this question, we examined the mice overexpressing Ikkβ (an essential component required for the activation of NF‐κB pathway) under the keratin 5 promoter (K5‐Ikkβ). Results: Upregulation of the NF‐κB pathway was confirmed in the ameloblasts of K5‐Ikkβ mice. Premature abrasion was observed in the molars of K5‐Ikkβ mice, which was accompanied by less mineralized enamel. However, no significant changes were observed in the enamel thickness and the pattern of enamel rods in K5‐Ikkβ mice. Klk4 expression was significantly upregulated in the ameloblasts of K5‐Ikkβ mice at the maturation stage, and the expression of its substrate, amelogenin, was remarkably reduced. This suggests that abnormal enamel observed in K5‐Ikkβ mice was likely due to the compromised degradation of enamel protein at the maturation stage. Conclusion: Therefore, we could conclude that the overactivation of the NF‐κB pathway impairs the process of amelogenesis.
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Ectodermal dysplasia (ED) is a genetically inherited syndrome caused by mutations affecting ectodermal tissue development, often resulting in hypodontia or anodontia accompanied by severe alveolar bone deficiency.
“Ectodermal dysplasia (ED) is a genetically inherited syndrome caused by mutations affecting ectodermal tissue development, often resulting in hypodontia or anodontia accompanied by severe alveolar bone deficiency [1–3].”
From Implant-supported fixed prosthodontic treatment for ectodermal dysplasia: a case report (2026) · cites this paper as [2]
The Introduction describes ectodermal dysplasia as a group of hereditary disorders affecting ectoderm-derived organs and links forms of hypohidrotic ectodermal dysplasia to gene mutations. It also lists hypodontia and anodontia among patients’ dental abnormalities. Neither the Introduction nor the additional passages found on alveolar bone address the claimed severe alveolar bone deficiency. (LLM, conf=0.88)
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- Authors
- Yamada, A., Kawasaki, M., Miake, Y., Yamada, Y., Blackburn, J., Kawasaki, K., Trakanant, S., Nagai, T., Nihara, J., Kudo, T., Meguro, F., Schmidt‐Ullrich, R., Liu, B., Hu, Y., Page, A., Ramírez, Á., Sharpe, P. T., Maeda, T., Takagi, R., & Ohazama, A.
- Affiliations
- Niigata University (JP)
- Tsurumi University (JP)
- King's College London (GB)
- Max Delbrück Center (DE)
- The University of Texas MD Anderson Cancer Center (US)
- National Cancer Institute (US)
- Research Institute Hospital 12 de Octubre (ES)
- Molecular Oncology Unit Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT) Instituto de Investigación Sanitaria Hospital12 de Octubre (imas12) CIBERONC Madrid Spain
- Corresponding author
- Ohazama, Atsushi
- ORCID
- Venue
- Oral Diseases
- Publisher
- Wiley
- Published
- 2020-07-09
- Volume
- 26
- Issue
- 7
- Pages
- 1513-1522
- ISSN
- 1354-523X (ISSN-L)
- 1601-0825
- PMC
- PMC8921976
- OpenAlex
- W3022658250
- Cited by
- 9
- References
- 46
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oral Diseases (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (26293421)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- NF-κB signaling, hypohidrotic ectodermal dysplasia, amelogenesis, molar enamel, keratin 5 promoter, ameloblasts, KLK4, amelogenin, enamel mineralization
- MeSH terms
- Ameloblasts, Amelogenesis, Animals, Dental Enamel, Humans, Molar, NF-kappa B, Mice
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