METTL3‐Mediatedm6A mRNAMethylation Modulates Tooth Root Formation by AffectingNFICTranslation

Autor: Rui Sheng, Jun Wang, Danting Zhang, Yunshu Wu, Qiwen Li, Shuang Jiang, Yuan Wang, Qingyue Xiao, Xingying Qi, Quan Yuan, Shiwen Zhang
Rok vydání: 2020
Předmět:
Zdroj: Journal of Bone and Mineral Research. 36:412-423
ISSN: 1523-4681
0884-0431
Popis: N6-methyladenosine (m6 A), as a eukaryotic mRNA modification catalyzed by methyltransferase METTL3, is involved in various processes of development or diseases via regulating RNA metabolism. However, the effect of METTL3-mediated m6 A modification in tooth development has remained elusive. Here we show that METTL3 is prevalently expressed in odontoblasts, dental pulp cells, dental follicle cells, and epithelial cells in Hertwig's epithelial root sheath during tooth root formation. Depletion of METTL3 in human dental pulp cells (hDPCs) impairs proliferation, migration, and odontogenic differentiation. Furthermore, conditional knockout of Mettl3 in Osterix-expressing cells leads to short molar roots and thinner root dentin featured by decreased secretion of pre-dentin matrix and formation of the odontoblast process. Mechanistically, loss of METTL3 cripples the translational efficiency of the key root-forming regulator nuclear factor I-C (NFIC). The odontogenic capacity of METTL3-silenced hDPCs is partially rescued via overexpressing NFIC. Our findings suggest that m6 A methyltransferase METTL3 is crucial for tooth root development, uncovering a novel epigenetic mechanism in tooth root formation. © 2020 American Society for Bone and Mineral Research (ASBMR).
Databáze: OpenAIRE
Externí odkaz: