title: Inorganic polyphosphates stimulate FGF23 expression through the FGFR pathway.
abstract: Polyphosphate (polyP) is composed of linear polymers of orthophosphate residues linked by high-energy phosphoanhydride bonds. It has been reported to improve osteoblastic differentiation, stimulate periodontal tissue regeneration, and accelerate bone repair. The aim of this study was to evaluate the effect of polyP on the expression of FGF23, a hormone secreted mostly be mature osteoblasts and osteocytes. In this study, different types of polyP were synthesized and co-cultured with osteoblast-like UMR-106 cells. Real-time PCR and western blot were used to analyze the gene and protein expression of FGF23. We found that 1 mM polyP was able to increase FGF23 expression after 4 h, reaching a peak after 12-24 h, with expression decreasing by 48 h. We also found that polyP could activate the FGFR pathway, as evidenced by increased phosphorylation of FGFR, FRS2, and Erk1/2. When FGFR signaling was inhibited by the specific inhibitor SU5402, the effect of polyP on FGF23 expression was significantly reduced. Our results indicate that polyP is able to stimulate osteoblastic FGF23 expression and that this effect is associated with activation of the FGFR pathway. These findings provide support for the clinical use of polyP by indicating a mechanism for polyP in bone regeneration.
authors.affiliation: State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, PR China.
authors.forename: Ningyuan
authors.initials: N
authors.lastname: Sun
authors.forename: Huawei
authors.initials: H
authors.lastname: Zou
authors.forename: Liang
authors.initials: L
authors.lastname: Yang
authors.forename: Koji
authors.initials: K
authors.lastname: Morita
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Shiba
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Akagawa
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010011:Osteocytes / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D011122:Polyphosphates / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D051496:Receptor, Fibroblast Growth Factor, Type 1; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000717427:FGF23 protein, human; C106534:FRS2 protein, human; D008565:Membrane Proteins; D011122:Polyphosphates; D011758:Pyrroles; C105686:SU 5402; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D011505:Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1