scholarly journals Overexpression of Fibroblast Growth Factor 23 Suppresses Osteoblast Differentiation and Matrix Mineralization In Vitro

2008 ◽  
Vol 23 (6) ◽  
pp. 939-948 ◽  
Author(s):  
Hua Wang ◽  
Yuji Yoshiko ◽  
Ryoko Yamamoto ◽  
Tomoko Minamizaki ◽  
Katsuyuki Kozai ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Osteoblast Differentiation ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Matrix Mineralization

scholarly journals Glucocorticoids dexamethasone and prednisolone suppress fibroblast growth factor 23 (FGF23)

2021 ◽  
Author(s):  
Martina Feger ◽  
Franz Ewendt ◽  
Jörg Strotmann ◽  
Holger Schäffler ◽  
Daniela Kempe-Teufel ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Iron Status ◽  
Fibroblast Growth Factor 23 ◽  
List Type ◽  
Fibroblast Growth ◽  
Active Vitamin ◽  
Active Vitamin D

Abstract Fibroblast growth factor 23 (FGF23) is a hormone mainly secreted by bone cells. Its most prominent effects are the regulation of renal phosphate reabsorption and calcitriol (active vitamin D, 1,25(OH)2D3) formation, effects dependent on its co-receptor αKlotho. Besides these actions, further paracrine and endocrine effects exist. The production of FGF23 is regulated by 1,25(OH)2D3, parathyroid hormone, dietary phosphate intake, iron status, as well as inflammation. Glucocorticoids are hormones with anti-inflammatory properties and are, therefore, widely used for acute and chronic inflammatory diseases, autoimmune disorders, and malignancies. The present study explored whether glucocorticoids influence the production of FGF23 in vitro as well as in mice. Fgf23 transcription was analyzed by semi-quantitative real-time PCR. Serum concentrations of FGF23 and 1,25(OH)2D3 were measured by ELISA. Urinary phosphate and Ca2+ excretion were determined in metabolic cages. As a result, in UMR106 rat osteoblast-like cells and in MC3T3-E1 cells, both, dexamethasone and prednisolone, downregulated Fgf23 transcription and FGF23 protein synthesis. Dexamethasone increased Dmp1 and Phex (encoding FGF23-regulating genes) as well as Nfkbia (encoding NFκB inhibitor IκBα) transcription in UMR106 cells. In mice, a single injection of dexamethasone or prednisolone was followed by a significant decrease of serum C-terminal and intact FGF23 concentration and bone Fgf23 mRNA expression within 12 h. These effects were paralleled by increased renal phosphate excretion and enhanced 1,25(OH)2D3 formation. We conclude that a single glucocorticoid treatment strongly downregulates the FGF23 plasma concentration. Key messages Glucocorticoids dexamethasone and prednisolone suppress the formation of bone-derived hormone fibroblast growth factor 23 (FGF23) in vitro. The effect is accompanied by an upregulation of Dmp1, Phex, and IκBα, negative regulators of FGF23, in UMR106 osteoblast-like cells. Glucocorticoid receptor antagonist RU-486 attenuates the effect of dexamethasone on FGF23, Dmp1, and Phex. In mice, a single glucocorticoid dose suppresses FGF23 and enhances 1,25(OH)2D3 (active vitamin D).

scholarly journals 1α,25-dihydroxyvitamin D3 acts predominately in mature osteoblasts under conditions of high extracellular phosphate to increase fibroblast growth factor 23 production in vitro

2010 ◽  
Vol 206 (3) ◽  
pp. 279-286 ◽  
Author(s):  
Ryoko Yamamoto ◽  
Tomoko Minamizaki ◽  
Yuji Yoshiko ◽  
Hirotaka Yoshioka ◽  
Kazuo Tanne ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Fibroblast Growth ◽  
Dihydroxyvitamin D3 ◽  
Osteoblast Development

Osteoblasts/osteocytes are the principle sources of fibroblast growth factor 23 (FGF23), a phosphaturic hormone, but the regulation of FGF23 expression during osteoblast development remains uncertain. Because 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and inorganic phosphate (Pi) may act as potent activators of FGF23 expression, we estimated how these molecules regulate FGF23 expression during rat osteoblast development in vitro. 1,25(OH)2D3-dependent FGF23 production was restricted largely to mature cells in correlation with increased vitamin D receptor (VDR) mRNA levels, in particular, when Pi was present. Pi alone and more so in combination with 1,25(OH)2D3 increased FGF23 production and VDR mRNA expression. Parathyroid hormone, stanniocalcin 1, prostaglandin E2, FGF2, and foscarnet did not increase FGF23 mRNA expression. Thus, these results suggest that 1,25(OH)2D3 may exert its largest effect on FGF23 expression/production when exposed to high levels of extracellular Pi in osteoblasts/osteocytes.

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