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Overexpression of constitutively active MAP3K7 in ameloblasts causes enamel defects of mouse teeth
Zhao Jinping1, Chu Qing1, Song Wenying1
1Department of Stomatology, Hospital Affiliated to Binzhou Medical University, Binzhou City, Shandong Province 256603, People's Republic of China.
Objective:
Compelling evidence suggests that mitogen-activated protein kinases (Mapks) play an important role in amelogenesis. However, the role of transforming growth factor (TGF)-β-activating kinase 1 (Tak1, Map3k7), which is a known upstream kinase of Mapks, during amelogenesis remains to be determined. The aim of this study was to investigate the possible involvement of Map3k7 in amelogenesis.
Design:
We generated transgenic mice that produced constitutively active human MAP3K7 (caMAP3K7) under the control of amelogenin (Amelx) gene promoter. Radiography and micro-computed tomography (μCT) analysis was used to detect the radio-opacity and density of the teeth. The enamel microstructure was observed with a scanning electron microscope. Histological analysis was used to observe the adhesion between ameloblasts and residual organic matrix of the enamel. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of enamel matrix protein.
Results:
The enamel of mandibular molars in caMAP3K7-overexpressing mice displayed pigmentation and a highly irregular structure compared with the wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. The gross histological appearances of ameloblasts and supporting cellular structures, as well as the expression of the enamel protein amelotin (Amtn) were altered by the overexpression of caMAP3K7.
Conclusions:
Our data demonstrated that protein expression, processing and secretion occurred abnormally in transgenic mice overexpressing caMAP3K7. The overexpression of caMAP3K7 had a profound effect on enamel structure by disrupting the orderly growth of enamel prisms.
Insights
Overexpressing transforming growth factor (TGF)-β-activating kinase 1 (Tak1, Map3k7) in mice disrupts enamel formation, leading to abnormal tooth structure and function. This study reveals Tak1
Area of Science:
- Dental research
- Molecular biology
- Developmental biology
Background:
- Mitogen-activated protein kinases (Mapks) are crucial for amelogenesis.
- Transforming growth factor (TGF)-β-activating kinase 1 (Tak1, Map3k7) is an upstream kinase of Mapks.
- The specific role of Tak1 in amelogenesis is not well understood.
Purpose of the Study:
- To investigate the involvement of Map3k7 in the process of tooth enamel formation (amelogenesis).
Main Methods:
- Generated transgenic mice with constitutively active human MAP3K7 (caMAP3K7) under the amelogenin (Amelx) promoter.
- Utilized radiography, micro-computed tomography (μCT), scanning electron microscopy, and histological analysis.
- Analyzed enamel microstructure, tooth density, and expression of enamel matrix proteins via qRT-PCR.
Main Results:
- Overexpression of caMAP3K7 in mice resulted in pigmented and structurally irregular enamel.
- Transgenic teeth exhibited rapid attrition due to enamel brittleness and disorganized hydroxyapatite crystal arrangement.
- Histological analysis revealed alterations in ameloblasts, supporting cells, and amelotin (Amtn) expression.
Conclusions:
- Abnormal protein expression, processing, and secretion were observed in transgenic mice overexpressing caMAP3K7.
- Tak1 overexpression significantly impacts enamel structure by disrupting the organized growth of enamel prisms.