caa a22 4500 605520429 CHVBK 20210128100735.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00223-015-0013-6 doi (NATIONALLICENCE)springer-10.1007/s00223-015-0013-6 Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology [Elektronische Daten] [Lise Allard, Nathalie Demoncheaux, Irma Machuca-Gayet, Dan Georgess, Fabienne Coury-Lucas, Pierre Jurdic, Justine Bacchetta] 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. Springer Science+Business Media New York, 2015 Bone resorption nationallicence Differentiation nationallicence FGF23 nationallicence Human nationallicence Osteoclast nationallicence Vitamin D nationallicence Allard Lise Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut Demoncheaux Nathalie Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut Machuca-Gayet Irma Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut Georgess Dan Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut Coury-Lucas Fabienne Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut Jurdic Pierre Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut Bacchetta Justine Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/1(2015-07-01), 69-79 0171-967X 97:1<69 2015 97 223 https://doi.org/10.1007/s00223-015-0013-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-0013-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Allard Lise Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut NATIONALLICENCE 700 1- Demoncheaux Nathalie Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut NATIONALLICENCE 700 1- Machuca-Gayet Irma Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut NATIONALLICENCE 700 1- Georgess Dan Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut NATIONALLICENCE 700 1- Coury-Lucas Fabienne Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut NATIONALLICENCE 700 1- Jurdic Pierre Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut NATIONALLICENCE 700 1- Bacchetta Justine Institut de Génomique Fonctionnelle de Lyon, ENS UMR 5242, Université de Lyon, Lyon, France aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/1(2015-07-01), 69-79 0171-967X 97:1<69 2015 97 223