| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
Soluble Klotho causes hypomineralization in Klotho-deficient mice |
|
言語 |
en |
| 作成者 |
Minamizaki, Tomoko
Konishi, Yukiko
Sakurai, Kaoru
Yoshioka, Hirotaka
Aubin, Jane E.
Kozai, Katsuyuki
Yoshiko, Yuji
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
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。 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
FGF23 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Klotho |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
Phex |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
kl/kl mice |
| 主題 |
|
|
主題Scheme |
NDC |
|
主題 |
490 |
| 内容記述 |
|
|
内容記述 |
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. |
|
言語 |
en |
| 内容記述 |
|
|
内容記述タイプ |
Other |
|
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). |
| 出版者 |
|
|
出版者 |
Society for Endocrinology |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
AO |
|
出版タイプResource |
http://purl.org/coar/version/c_b1a7d7d4d402bcce |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1530/JOE-17-0683 |
| 関連情報 |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
29632215 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1530/JOE-17-0683 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0022-0795 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1479-6805 |
| 開始ページ |
|
|
開始ページ |
285 |
| 書誌情報 |
Journal of Endocrinology
Journal of Endocrinology
巻 237,
号 3,
p. 285-300,
発行日 2018-06
|
| 旧ID |
49037 |
| 備考 |
Post-print version/PDF may be used in an institutional repository after an embargo period of 12 months. |
JEndocrinol_237_285.pdf (1.5 MB)
