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Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology | Calcified Tissue International
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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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Keywords {đ}
pubmed, article, google, scholar, cas, bone, fgf, central, osteoclast, human, vitamin, bacchetta, res, effects, differentiation, osteoclasts, fibroblast, growth, factor, miner, allard, justine, resorption, activity, clin, lyon, privacy, cookies, content, research, lise, machucagayet, osteoclastogenesis, kidney, phosphate, invest, wang, france, data, publish, search, tissue, demoncheaux, irma, georgess, fabienne, courylucas, role, experiments, access,
Topics {âïž}
ifn-beta-dependent nfatc1 suppression month download article/chapter pÎle femme-mÚre-enfant fabienne coury-lucas mitogen-activated protein kinase justine bacchetta declare human monocyte-derived osteoclasts service de néphrologie serum phosphate-independent functions bone-resorbing osteoclast activity full article pdf control bone resorption chronic kidney disease systemic phosphate homeostasis master research project université de lyon justine bacchetta article allard calcium/phosphate balance human osteoclast biology privacy choices/manage cookies razzaque ms pereira rc wesseling-perry mineralized tissue cells pierre jurdic related subjects anti-osteoclastogenic action fgf23 transgenic mice c-fos protein irma machuca-gayet european economic area western blot analyses distal convoluted tubule rheumatoid arthritis microenvironment azucena-serrano ce inhibiting osteoclast formation renal phosphate transport significantly inhibited osteoclastogenesis kidney transplant loss therapies modulating fgf23 article log fgf23-mediated regulation conditions privacy policy accepting optional cookies klotho gene family acknowledge marlene mazzorana article cite osteoclast physiology biochemical experiments showed
Questions {â}
- Razzaque MS (2009) FGF23-mediated regulation of systemic phosphate homeostasis: is Klotho an essential player?
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headline:Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology
description: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.
datePublished:2015-05-19T00:00:00Z
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Differentiation
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Vitamin D
Biochemistry
general
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Cell Biology
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headline:Biphasic Effects of Vitamin D and FGF23 on Human Osteoclast Biology
description: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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Differentiation
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Human
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Vitamin D
Biochemistry
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