このエントリーをはてなブックマークに追加
ID 49037
本文ファイル
著者
Minamizaki, Tomoko 大学院医歯薬保健学研究科(歯) 広大研究者総覧
Konishi, Yukiko 大学院医歯薬保健学研究院(歯)
Sakurai, Kaoru 病院(歯)
Yoshioka, Hirotaka 大学院医歯薬保健学研究院(歯)
Aubin, Jane E.
Kozai, Katsuyuki 大学院医系科学研究科(歯) 広大研究者総覧
Yoshiko, Yuji 大学院医系科学研究科(歯) 広大研究者総覧
キーワード
FGF23
Klotho
Phex
kl/kl mice
NDC
医学
抄録(英)
The type I transmembrane protein αKlotho (Klotho) serves as a coreceptor for the phosphaturic hormone fibroblast growth factor 23 (FGF23) in kidney, while a truncated form of Klotho (soluble Klotho, sKL) is thought to exhibit multiple activities, including acting as a hormone, but whose mode(s) of action in different organ systems remains to be fully elucidated. FGF23 is expressed primarily in osteoblasts/osteocytes and aberrantly high levels in the circulation acting via signaling through an FGF receptor (FGFR)-Klotho coreceptor complex cause renal phosphate wasting and osteomalacia. We assessed the effects of exogenously added sKL on osteoblasts and bone using Klotho-deficient (kl/kl) mice and cell and organ cultures. sKL induced FGF23 signaling in bone and exacerbated the hypomineralization without exacerbating the hyperphosphatemia, hypercalcemia and hypervitaminosis D in kl/kl mice. The same effects were seen in rodent bone models in vitro, in which we also detected formation of a sKL complex with FGF23-FGFR and decreased Phex (gene responsible for X-linked hypophosphatemic rickets (XLH)/osteomalacia) expression. Further, sKL-FGF23-dependent hypomineralization in vitro was rescued by soluble PHEX. These data suggest that exogenously added sKL directly participates in FGF23 signaling in bone and that PHEX is a downstream effector of the sKL-FGF23-FGFR axis in bone.
内容記述
This work was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (18592001 and 20592139 to Y Y and 21791788 to T M), and the Canadian Institutes of Health Research (MOP 83704 to J E A).
掲載誌名
Journal of Endocrinology
237巻
3号
開始ページ
285
終了ページ
300
出版年月日
2018-06
出版者
Society for Endocrinology
ISSN
0022-0795
1479-6805
出版者DOI
PubMedID
言語
英語
NII資源タイプ
学術雑誌論文
広大資料タイプ
学術雑誌論文
DCMIタイプ
text
フォーマット
application/pdf
著者版フラグ
author
権利情報
This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Endocrinology, copyright © Society for Endocrinology after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1530/JOE-17-0683. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認、ご利用ください。
関連情報URL
部局名
医歯薬保健学研究科
病院
備考
Post-print version/PDF may be used in an institutional repository after an embargo period of 12 months.