Soluble Klotho causes hypomineralization in Klotho-deficient mice

• Minamizaki, Tomoko

• Konishi, Yukiko

• Sakurai, Kaoru

• Yoshioka, Hirotaka

• Aubin, Jane E.

• Kozai, Katsuyuki

• Yoshiko, Yuji

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.

収録刊行物

• Journal of Endocrinology

  Journal of Endocrinology 237 (3), 285-300, 2018-06

  Society for Endocrinology

キーワード

• FGF23
• Klotho
• Phex
• kl/kl mice

詳細情報

• CRID: 1050296265984292480
• NII論文ID: 120006826841
• Web Site: http://ir.lib.hiroshima-u.ac.jp/00049037
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles