Blocking FGF23 signaling improves the growth plate of mice with X-linked hypophosphatemia

in Journal of Endocrinology
Authors:
Rocío Fuente Institute of Physiology, University of Zurich, and National Center of Competence in Research NNCR Kidney, Zurich, CH, Switzerland
Division of Pediatrics, University of Oviedo, Oviedo, Spain
Department of Pediatrics, Hospital Universitario Central, Oviedo, Spain

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Eva-Maria Pastor-Arroyo Institute of Physiology, University of Zurich, and National Center of Competence in Research NNCR Kidney, Zurich, CH, Switzerland

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Nicole Gehring Institute of Physiology, University of Zurich, and National Center of Competence in Research NNCR Kidney, Zurich, CH, Switzerland

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Patricia Oro Carbajosa Division of Pediatrics, University of Oviedo, Oviedo, Spain

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Laura Alonso-Durán Division of Pediatrics, University of Oviedo, Oviedo, Spain

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Ivan Zderic AO Research Institute Davos, AO Foundation, Clavadelerstrasse, Davos Platz, Switzerland

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James Tapia-Dean Department of Pediatrics, Hospital Universitario Central, Oviedo, Spain

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Ahmad Kamal Hamid Institute of Physiology, University of Zurich, and National Center of Competence in Research NNCR Kidney, Zurich, CH, Switzerland

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Carla Bettoni Institute of Physiology, University of Zurich, and National Center of Competence in Research NNCR Kidney, Zurich, CH, Switzerland

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Fernando Santos Division of Pediatrics, University of Oviedo, Oviedo, Spain
Department of Pediatrics, Hospital Universitario Central, Oviedo, Spain

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Carsten A Wagner Institute of Physiology, University of Zurich, and National Center of Competence in Research NNCR Kidney, Zurich, CH, Switzerland

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Isabel Rubio-Aliaga Institute of Physiology, University of Zurich, and National Center of Competence in Research NNCR Kidney, Zurich, CH, Switzerland

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https://orcid.org/0000-0003-1051-9511

Correspondence should be addressed to C Wagner or I Rubio-Aliaga: carsten.wagner@physiol.uzh.ch or isabel.rubioaliaga@uzh.ch
DOI:
https://doi.org/10.1530/JOE-23-0025
Volume/Issue:
Volume 259: Issue 1
Article Type:
Research Article
Article ID:
e230025
Online Publication Date:
25 Aug 2023
Copyright:
© the author(s) 2023
Restricted access
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Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone. X-linked hypophosphatemia (XLH) is the most prevalent inherited phosphate wasting disorder due to mutations in the PHEX gene, which cause elevated circulating FGF23 levels. Clinically, it is characterized by growth impairment and defective mineralization of bones and teeth. Treatment of XLH is challenging. Since 2018, neutralizing antibodies against FGF23 have dramatically improved the therapy of XLH patients, although not all patients fully respond to the treatment, and it is very costly. C-terminal fragments of FGF23 have recently emerged as blockers of intact FGF23 signaling. Here, we analyzed the effect on growth and bone of a short 26 residues long C-terminal FGF23 (cFGF23) fragment and two N-acetylated and C-amidated cFGF23 peptides using young XLH mice (Phex C733RMhda mice). Although no major changes in blood parameters were observed after 7 days of treatment with these peptides, bone length and growth plate structure improved. The modified peptides accelerated the growth rate probably by improving growth plate structure and dynamics. The processes of chondrocyte proliferation, death, hypertrophy, and the cartilaginous composition in the growth plate were partially improved in young treated XLH mice. In conclusion, these findings contribute to understand the role of FGF23 signaling in growth plate metabolism and show that this may occur despite continuous hypophosphatemia.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2023
Article ID:
e230025
Article Type:
Research Article
Received Date:
24 Jan 2023
Accepted Date:
12 Jul 2023
Print Publication Date:
01 Sep 2023
Online Publication Date:
25 Aug 2023
Keywords:
XLH; FGF23; bone mass density; growth plate; growth

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