title: Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology.
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.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France.
authors.forename: Lise
authors.initials: L
authors.lastname: Allard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Demoncheaux
authors.forename: Irma
authors.initials: I
authors.lastname: Machuca-Gayet
authors.forename: Dan
authors.initials: D
authors.lastname: Georgess
authors.forename: Fabienne
authors.initials: F
authors.lastname: Coury-Lucas
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: Justine
authors.initials: J
authors.lastname: Bacchetta
mesh_terms: D001862:Bone Resorption / Q000188:drug therapy; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000717427:FGF23 protein, human; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D016173:Macrophage Colony-Stimulating Factor