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

Autor: Martina Feger, Franz Ewendt, Michael Föller
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Fibroblast growth factor 23
TGF-β
Physiology
Signaling and Cell Physiology
Pyridines
Activin Receptors
Clinical Biochemistry
030209 endocrinology & metabolism
Phosphate
Myostatin
Dioxoles
urologic and male genital diseases
p38 Mitogen-Activated Protein Kinases
Cell Line
03 medical and health sciences
Paracrine signalling
Mice
0302 clinical medicine
Physiology (medical)
Cell Line
Tumor
Myokine
medicine
Animals
Vitamin D
Activin Receptor Type-2B
Protein Kinase Inhibitors
Withanolides
Activin Receptor Type-2A
Osteoblasts
biology
Chemistry
Imidazoles
NF-kappa B
Osteoblast
musculoskeletal system
Cell biology
Rats
stomatognathic diseases
Ca2+
Fibroblast Growth Factor-23
030104 developmental biology
medicine.anatomical_structure
Benzamides
biology.protein
p38MAPK
Calcium
Transforming growth factor
Zdroj: Pflugers Archiv
ISSN: 1432-2013
0031-6768
Popis: Myostatin 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.
Databáze: OpenAIRE
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