title: Incisor enamel formation is impaired in transgenic rats overexpressing the type III NaPi transporter Slc20a1.
abstract: Inorganic phosphate (Pi) is required in many biological processes, including signaling cascades, skeletal development, tooth mineralization, and nucleic acid synthesis. Recently, we showed that Pi transport in osteoblasts, mediated by Slc20a1, a member of the type III sodium-dependent phosphate transporter family, is indispensable for osteoid mineralization in rapidly growing rat bone. In addition, we found that bone mineral density decreased slightly with dysfunction of Pi homeostasis in aged transgenic rats overexpressing mouse Slc20a1 (Slc20a1-Tg). Bone and tooth share certain common molecular features, and thus, we focused on tooth development in Slc20a1-Tg mandibular incisors in order to determine the role of Slc20a1 in tooth mineralization. Around the time of weaning, there were no significant differences in serologic parameters between wild-type and Slc20a1-Tg rats. However, histological analysis showed that Slc20a1-Tg ameloblasts formed clusters in the papillary layer during the maturation stage as early as 4 weeks of age. These pathologies became more severe with age and included the formation of cyst-like or multilayer ameloblast structures, accompanied by a chalky white appearance with abnormal attrition and fracture. Hyperphosphatemia was also observed in aging Slc20a1-Tg rats. Micro-computed tomography and electron probe microanalysis revealed impairments in enamel, such as delayed mineralization and hypomineralization. Our results suggest that enamel formation is sensitive to imbalances in Pit1-mediated cellular function as seen in bone, although these processes are under the control of systemic Pi homeostasis.
authors.affiliation: Department of Oral Growth and Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, Kasumi, Minamiku, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Yoshioka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiko
authors.forename: Tomoko
authors.initials: T
authors.lastname: Minamizaki
authors.forename: Sayaka
authors.initials: S
authors.lastname: Suzuki
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Koma
authors.forename: Asako
authors.initials: A
authors.lastname: Nobukiyo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sotomaru
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Itoh
authors.forename: Norihiko
authors.initials: N
authors.lastname: Maeda
mesh_terms: D000818:Animals; D003743:Dental Enamel / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D003744:Dental Enamel Hypoplasia / Q000235:genetics; D015870:Gene Expression; D007180:Incisor / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D051379:Mice; D051381:Rats; D055647:Rats, Transgenic; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000235:genetics* / Q000378:metabolism; D014074:Tooth Calcification / Q000235:genetics / Q000502:physiology; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology
chemical_list: C493587:Slc20a1 protein, mouse; D050611:Sodium-Phosphate Cotransporter Proteins, Type III