FGF receptors control vitamin D and phosphate homeostasis by mediating renal FGF-23 signaling and regulating FGF-23 expression in bone

• DOI: 10.1002/jbmr.478
• Publication Date: 2011-08-02T20:32:53Z
• Authors: Simon Wöhrle; Olivier Bonny; Noemie Beluch; Swann Gaulis; Christelle Stamm; Marcel Scheibler; Matthias Müller; Bernd Kinzel; Anne Thuery; Joseph Brueggen; Nancy E Hynes; William R Sellers; Francesco Hofmann; Diana Graus-Porta
• Keywords: Klotho; Homeostasis

Abstract The functional interaction between fibroblast growth factor 23 (FGF-23) and Klotho in the control of vitamin D phosphate homeostasis is manifested by largely overlapping phenotypes Fgf23- Klotho-deficient mouse models. However, to date, targeted inactivation FGF receptors (FGFRs) has not provided clear evidence for an analogous function FGFRs this process. Here, means pharmacologic inhibition FGFRs, we demonstrate their involvement renal FGF-23/Klotho signaling elicit role homeostasis. Specifically, FGFR loss counteracts signaling, leading deregulation Cyp27b1 Cyp24a1 induction hypervitaminosis hyperphosphatemia. In turn, initiates a feedback response high serum levels FGF-23. Further, show that blocks Fgf23 transcription bone dominant over D–induced expression, ultimately impinging on systemic FGF-23 protein levels. Additionally, identify as specific target gene vitro. Thus, line with models, our study illustrates essential regulation reveal novel vivo mechanism expression bone, suggesting dual pathway © 2011 American Society Bone Mineral Research