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 1mM polyP was able to increase FGF23 expression after 4h, reaching a peak after 12–24h, with expression decreasing by 48h. 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. [Copyright &y& Elsevier]