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Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology

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Abstract

Vitamin D and FGF23 play a major role in calcium/phosphate balance. Vitamin D may control bone resorption but the potential role of FGF23 has never been evaluated. The objective of this study was therefore to compare the effects of vitamin D and FGF23 on osteoclast differentiation and activity in human monocyte-derived osteoclasts. Human monocytes, purified from blood of healthy donors, were incubated with M-CSF and RANKL to obtain mature multinucleated osteoclasts (MNC). Experiments were carried out to assess the effects of FGF23 as compared to native vitamin D (25-D) and active vitamin D (1,25-D) on osteoclast differentiation and on bone-resorbing osteoclast activity. Additional experiments with the pan fibroblast growth factor receptor inhibitor (FGFR-i) were performed. Phosphorylation Akt and Erk pathways were analyzed by Western blot analyses. Both 1,25-D and FGF23, to a lesser extent, significantly inhibited osteoclastogenesis at early stages; when adding FGFR-i, osteoclast formation was restored. Biochemical experiments showed an activation of the Akt and Erk pathways under FGF23 treatment. In contrast, in terms of activity, 1,25-D had no effect on resorption, whereas FGF23 slightly but significantly increased bone resorption; 25-D had no effects on either differentiation or on activity. These data show that 1,25-D inhibits osteoclastogenesis without regulating osteoclast-mediated bone resorption activity; FGF23 has biphasic effects on osteoclast physiology, inhibiting osteoclast formation while stimulating slightly osteoclast activity. These results may be of importance and taken into account in chronic kidney disease when therapies modulating FGF23 are available.

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Acknowledgments

Lise Allard received an educational grant from the French Society of Pediatric Endocrinology and Diabetology for her master research project. A financial support was provided by Amgen, Sandoz and by la Fondation du Rein/Prix Jeune Chercheur 2013 (JB) for reagents and experiments. The authors would like to acknowledge Marlene Mazzorana, PhD, for her skillful technical help for the purification of monocytes and cell cultures.

Conflict of interest

Lise Allard, Nathalie Demoncheaux, Irma Machuca-Gayet, Dan Georgess, Fabienne Coury-Lucas, Pierre Jurdic and Justine Bacchetta declare that they have they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human participants or animals performed by any of the authors. Blood samples from healthy adult volunteer donors were purchased from the Etablissement Français du Sang, Site Gerland, Lyon, France.

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Authors and Affiliations

  1. Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France

    Lise Allard, Nathalie Demoncheaux, Irma Machuca-Gayet, Dan Georgess, Fabienne Coury-Lucas, Pierre Jurdic & Justine Bacchetta

  2. Service de Pédiatrie, Pôle Femme-Mère-Enfant, CHU d’Angers, 49003, Angers, France

    Lise Allard

  3. INSERM 1033, 69008, Lyon, France

    Irma Machuca-Gayet, Fabienne Coury-Lucas & Justine Bacchetta

  4. Centre de Référence des Maladies Rénales Rares, Service de Néphrologie et Rhumatologie Pédiatriques, Hospices Civils de Lyon, Hôpital Femme Mère Enfant, 59 Bd Pinel, 69677, Bron Cedex, France

    Justine Bacchetta

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  1. Lise Allard
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  2. Nathalie Demoncheaux
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Correspondence to Justine Bacchetta.

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Allard, L., Demoncheaux, N., Machuca-Gayet, I. et al. Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology. Calcif Tissue Int 97, 69–79 (2015). https://doi.org/10.1007/s00223-015-0013-6

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  • DOI: https://doi.org/10.1007/s00223-015-0013-6

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