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Incisor Enamel Formation is Impaired in Transgenic Rats Overexpressing the Type III NaPi Transporter Slc20a1

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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.

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Acknowledgments

We thank Akifumi Kanda, Chika Kosako, and Miyuki Yoshioka for animal maintenance and genotyping. We are also grateful to Hayami Ishisako for the preparation of EPMA samples and Yasuhiro Shibata for conducting the EPMA. This work was supported by the Japan Society for the Promotion of Science (Grants-in-Aid for Young Scientists 21890156 and 22791768 to H. Y., and Grants-in-Aid for Scientific Research 18592001 and 20592139 to Y. Y.).

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Authors and Affiliations

  1. Department of Oral Growth and Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8553, Japan

    Hirotaka Yoshioka, Yuji Yoshiko, Tomoko Minamizaki, Sayaka Suzuki, Yoshiro Koma & Norihiko Maeda

  2. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan

    Asako Nobukiyo & Yusuke Sotomaru

  3. Division of Endocrinology and Metabolism, Department of Internal Medicine, Fujita Health University, Toyoake, Japan

    Atsushi Suzuki & Mitsuyasu Itoh

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  1. Hirotaka Yoshioka
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Correspondence to Yuji Yoshiko.

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Yoshioka, H., Yoshiko, Y., Minamizaki, T. et al. Incisor Enamel Formation is Impaired in Transgenic Rats Overexpressing the Type III NaPi Transporter Slc20a1. Calcif Tissue Int 89, 192–202 (2011). https://doi.org/10.1007/s00223-011-9506-0

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