326 1α,25-DIHYDROXYVITAMIN D3 UP-REGULATES FIBROBLAST GROWTH FACTOR 23 GENE EXPRESSION IN A RAT OSTEOBLASTIC CELL LINE AND MOUSE CALVARIA

2005 ◽  
Vol 53 (1) ◽  
pp. S135.3-S135
Author(s):  
O. I. Kolek ◽  
E. R. Hines ◽  
M. D. Jones ◽  
L. LeSueur ◽  
P. R. Kiela ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Line ◽  
Fibroblast Growth Factor 23 ◽  
Osteoblastic Cell ◽  
Fibroblast Growth ◽  
Dihydroxyvitamin D3 ◽  
Osteoblastic Cell Line ◽  
Mouse Calvaria

scholarly journals Bone Formation Regulates Circulating Concentrations of Fibroblast Growth Factor 23

Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 4835-4845 ◽  
Author(s):  
Rana Samadfam ◽  
Christian Richard ◽  
Loan Nguyen-Yamamoto ◽  
Isabel Bolivar ◽  
David Goltzman
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Turnover ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Negative Regulator ◽  
Fibroblast Growth ◽  
Osteoblastic Cell Line ◽  
High Calcium

We examined the role of bone remodeling in the regulation of circulating concentrations of FGF23 using mouse models manifesting differing degrees of coupled and uncoupled bone turnover. Administration of the antiresorptive agent osteoprotegerin produced a profound reduction in bone resorption and formation in male and oophorectomized female mice, accompanied by an increase in serum levels of fibroblast growth factor 23 (FGF23) and a reduction in circulating 1,25-dihydroxyvitamin D [1,25(OH)2D]. In contrast, exogenous PTH(1-34) administration increased bone turnover and reduced circulating FGF23. In 1,25(OH)2D-deficient, 25-hydroxyvitamin D 1α-hydroxylase null mice on a high-calcium diet, endogenous PTH was elevated, bone formation but not resorption was increased, and serum FGF23 was virtually undetectable; on a rescue diet, serum calcium was normalized, PTH levels were reduced, bone formation was reduced, and serum FGF23 levels increased. After PTH treatment of wild-type mice, gene expression of dentin matrix protein 1 (DMP1) in bone was increased, whereas gene expression of FGF23 was reduced. In vitro studies in the osteoblastic cell line UMR-106 showed that externally added DMP1 could inhibit FGF23 gene expression and production stimulated by 1,25(OH)2D3. The results show that osteoblastic bone formation is a potent modulator of FGF23 production and release into the circulation, suggest that the biological consequences on mineral homeostasis of circulating FGF23 may also be dependent on the prevailing rate of bone turnover, and provide evidence that DMP1 may be a direct negative regulator of FGF23 production in osteoblastic cells.

scholarly journals Transgenic Mice Overexpressing Human Fibroblast Growth Factor 23 (R176Q) Delineate a Putative Role for Parathyroid Hormone in Renal Phosphate Wasting Disorders

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 5269-5279 ◽  
Author(s):  
Xiuying Bai ◽  
Dengshun Miao ◽  
Jiarong Li ◽  
David Goltzman ◽  
Andrew C. Karaplis
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Fibroblast Growth Factor ◽  
Calcium Homeostasis ◽  
Fibroblast Growth Factor 23 ◽  
Fibroblast Growth ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Circulating Levels

Abstract Fibroblast growth factor 23 (FGF23) is a recently characterized protein likely involved in the regulation of serum phosphate homeostasis. Increased circulating levels of FGF23 have been reported in patients with renal phosphate-wasting disorders, but it is unclear whether FGF23 is the direct mediator responsible for the decreased phosphate transport at the proximal renal tubules and the altered vitamin D metabolism associated with these states. To examine this question, we generated transgenic mice expressing and secreting from the liver human FGF23 (R176Q), a mutant form that fails to be degraded by furin proteases. At 1 and 2 months of age, mice carrying the transgene recapitulated the biochemical (decreased urinary phosphate reabsorption, hypophosphatemia, low serum 1,25-dihydroxyvitamin D3) and skeletal (rickets and osteomalacia) alterations associated with these disorders. Unexpectantly, marked changes in parameters of calcium homeostasis were also observed, consistent with secondary hyperparathyroidism. Moreover, in the kidney the anticipated alterations in the expression of hydroxylases associated with vitamin D metabolism were not observed despite the profound hypophosphatemia and increased circulating levels of PTH, both major physiological stimuli for 1,25-dihydroxyvitamin D3 production. Our findings strongly support the novel concept that high circulating levels of FGF23 are associated with profound disturbances in the regulation of phosphate and vitamin D metabolism as well as calcium homeostasis and that elevated PTH levels likely also contribute to the renal phosphate wasting associated with these disorders.

scholarly journals Myostatin regulates the production of fibroblast growth factor 23 (FGF23) in UMR106 osteoblast–like cells

2021 ◽  
Author(s):  
Franz Ewendt ◽  
Martina Feger ◽  
Michael Föller
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Fibroblast Growth Factor 23 ◽  
Receptor Type ◽  
Type I ◽  
Fibroblast Growth ◽  
Activin Receptor

AbstractMyostatin is a signaling molecule produced by skeletal muscle cells (myokine) that inhibits muscle hypertrophy and has further paracrine and endocrine effects in other organs including bone. Myostatin binds to activin receptor type 2B which forms a complex with transforming growth factor-β type I receptor (TGF-βRI) and induces intracellular p38MAPK and NFκB signaling. Fibroblast growth factor 23 (FGF23) is a paracrine and endocrine mediator produced by bone cells and regulates phosphate and vitamin D metabolism in the kidney. P38MAPK and NFκB-dependent store-operated Ca2+ entry (SOCE) are positive regulators of FGF23 production. Here, we explored whether myostatin influences the synthesis of FGF23. Fgf23 gene expression was determined by qRT-PCR and FGF23 protein by ELISA in UMR106 osteoblast–like cells. UMR106 cells expressed activin receptor type 2A and B. Myostatin upregulated Fgf23 gene expression and protein production. The myostatin effect on Fgf23 was significantly attenuated by TGF-βRI inhibitor SB431542, p38MAPK inhibitor SB202190, and NFκB inhibitor withaferin A. Moreover, SOCE inhibitor 2-APB blunted the myostatin effect on Fgf23. Taken together, myostatin is a stimulator of Fgf23 expression in UMR106 cells, an effect at least partially mediated by downstream TGF-βRI/p38MAPK signaling as well as NFκB-dependent SOCE.

scholarly journals Up-Regulation of Fibroblast Growth Factor 23 Gene Expression in UMR106 Osteoblast-like Cells with Reduced Viability

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 40
Author(s):  
Sina Münz ◽  
Martina Feger ◽  
Bayram Edemir ◽  
Michael Föller
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Cellular Damage ◽  
Fibroblast Growth ◽  
Paracrine Effects ◽  
Signaling Inhibitors ◽  
Apoptosis And Necrosis

Fibroblast growth factor 23 (FGF23) controls vitamin D and phosphate homeostasis in the kidney and has additional paracrine effects elsewhere. As a biomarker, its plasma concentration is associated with progression of inflammatory, renal, and cardiovascular diseases. Major stimuli of FGF23 synthesis include active vitamin D and inflammation. Antineoplastic chemotherapy treats cancer by inducing cellular damage ultimately favoring cell death (apoptosis and necrosis) and causing inflammation. Our study explored whether chemotherapeutics and other apoptosis inducers impact on Fgf23 expression. Experiments were performed in osteoblast-like UMR106 cells, Fgf23 gene expression and protein synthesis were determined by qRT-PCR and ELISA, respectively. Viability was assessed by MTT assay and NFκB activity by Western Blotting. Antineoplastic drugs cisplatin and doxorubicin as well as apoptosis inducers procaspase-activating compound 1 (PAC-1), a caspase 3 activator, and serum depletion up-regulated Fgf23 transcripts while reducing cell proliferation and viability. The effect of cisplatin on Fgf23 transcription was paralleled by Il-6 up-regulation and NFκB activation and attenuated by Il-6 and NFκB signaling inhibitors. To conclude, cell viability-decreasing chemotherapeutics as well as apoptosis stimulants PAC-1 and serum depletion up-regulate Fgf23 gene expression. At least in part, Il-6 and NFκB may contribute to this effect.

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