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MFAP5 Activates ITGA5 to Drive Tooth Germ Mineralization Through the MAPK/ERK Pathway: Insights from Single-Cell
Xu Wang1,2, Lanxin Gu1,2, Ping Zhang1,2,3,4
1Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing 100081, China.
International Journal of Molecular Sciences
|January 10, 2026
Summary
Researchers identified microfibril-associated protein 5 (MFAP5) as a key regulator of tooth mineralization. MFAP5, through the ITGA5-ERK/MAPK pathway, is essential for odontoblast differentiation and dentin formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Biochemistry
Background:
- Tooth germ development involves complex cellular signaling.
- Regulatory mechanisms of tooth mineralization are not fully understood.
Purpose of the Study:
- To investigate molecular mechanisms of tooth mineralization using single-cell RNA sequencing.
- Identify novel regulators of odontogenic differentiation.
Main Methods:
- High-resolution single-cell RNA sequencing of miniature pig tooth germs.
- Functional assays to assess MFAP5's role in vitro.
- Analysis of gene expression and signaling pathways.
Main Results:
- Identified microfibril-associated protein 5 (MFAP5) as a novel regulator.
- MFAP5 is crucial for mesenchymal differentiation and matrix mineralization.
- MFAP5 interacts with Integrin alpha-5 (ITGA5) to activate ERK/MAPK signaling.
Conclusions:
- Uncovered a MFAP5-ITGA5-ERK/MAPK signaling axis in tooth germ mineralization.
- MFAP5 plays a cell-state-specific role in odontoblast differentiation and dentin deposition.
- Provides insights for dental tissue regeneration strategies.
