title: MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization.
abstract: Enamel mineralization is accompanied by the release of protons into the extracellular matrix, which is buffered to regulate the pH value in the local microenvironment. The present study aimed to investigate the role of microRNA 224 (miR-224) as a regulator of SLC4A4 and CFTR, encoding the key buffering ion transporters, in modulating enamel mineralization. miR-224 was significantly downregulated as ameloblasts differentiated, in parallel with upregulation of SLC4A4 and CFTR. Overexpression of miR-224 downregulated SLC4A4 and CFTR expression in cultured human epithelial cells. A microRNA luciferase assay confirmed the specific binding of miR-224 to the 3' untranslated regions (UTRs) of SLC4A4 and CFTR mRNAs, thereby inhibiting protein translation. miR-224 agomir injection in mouse neonatal incisors resulted in normal enamel length and thickness, but with disturbed organization of the prism structure and deficient crystal growth. Moreover, the enamel Ca/P ratio and microhardness were markedly reduced after miR-224 agomir administration. These results demonstrate that miR-224 plays a pivotal role in fine tuning enamel mineralization by modulating SLC4A4 and CFTR to maintain pH homeostasis and support enamel mineralization.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yachuan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Crane
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China zhenglw399@hotmail.com.
authors.forename: Liwei
authors.initials: L
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions; D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism*; D000566:Amelogenesis; D000818:Animals; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D003743:Dental Enamel / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics*; D014070:Tooth / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C498898:SLC4A4 protein, human; D027982:Sodium-Bicarbonate Symporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator