Soluble Klotho causes hypomineralization in Klotho-deficient mice

Journal of Endocrinology 237 巻 3 号 285-300 頁 2018-06 発行
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タイトル ( eng )
Soluble Klotho causes hypomineralization in Klotho-deficient mice
作成者
Aubin Jane E.
収録物名
Journal of Endocrinology
237
3
開始ページ 285
終了ページ 300
抄録
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.
著者キーワード
FGF23
Klotho
Phex
kl/kl mice
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).
NDC分類
医学 [ 490 ]
言語
英語
資源タイプ 学術雑誌論文
出版者
Society for Endocrinology
発行日 2018-06
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。
出版タイプ Author’s Original(十分な品質であるとして、著者から正式な査読に提出される版)
アクセス権 オープンアクセス
収録物識別子
[ISSN] 0022-0795
[ISSN] 1479-6805
[DOI] 10.1530/JOE-17-0683
[PMID] 29632215
[DOI] https://doi.org/10.1530/JOE-17-0683
備考 Post-print version/PDF may be used in an institutional repository after an embargo period of 12 months.