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 Protective Effects of Moderate Ca Supplementation against Cd-Induced Bone Damage under Different Population-Relevant Doses in Young Female Rats

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 849 ◽  
Author(s):  
Huang ◽  
Liu ◽  
Zhao ◽  
Fu ◽  
Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Young Female ◽  
Female Rats ◽  
Bone Biomechanics ◽  
Protective Effects ◽  
Fibroblast Growth ◽  
Bone Damage

Estimation of the skeleton-protective effects of Ca in Cd-induced bone damage is helpful in the assessment of Cd health risk. The aim of this study was to identify whether Ca supplementation during exposure to different population-relevant doses of Cd can prevent Cd-induced bone damage under the tolerable upper intake level of Ca supplementation. Young female Sprague-Dawley rats were given different population-relevant doses of Cd (1, 5, and 50 mg Cd/kg diet) and Ca supplementation (0.4% Ca supplementation) intervention. Ca supplementation significantly decreased Cd-induced bone microstructure damage, increased bone biomechanics (p < 0.05), serum bone formation marker level (p < 0.05) and expression of osteogenic gene markers exposure to the 5 and 50 mg Cd/kg diets. However, it had no impact on these indicators under the 1 mg Cd/kg diets, with the exception of expression of osteogenic marker genes. Ca supplementation significantly decreased serum Klotho level (p < 0.05), and fibroblast growth factor 23/Klotho-associated gene expression in the kidney and bone showed significant changes. In conclusion, Ca supplementation has a positive effect on bone formation and bone quality against the damaging impact of Cd, especially with exposure to the 5 mg and 50 mg Cd/kg diet, which may be related to its impact on the fibroblast growth factor 23/Klotho axis.

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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