Fibroblast growth factor 23 inhibits osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells

Abstract

Fibroblast growth factor 23 (FGF23), a bone-derived hormone, is involved in the reabsorption of phosphate (P) and the production of vitamin D hormones in the kidney. However, whether and how FGF23 regulates chicken bone metabolism remains largely unknown. In the present study, we investigated the effect of FGF23 on osteogenic differentiation and mineralization of chicken bone marrow mesenchymal stem cells (BMSCs). First, we found that the transcription of FGF23 was inhibited by β-glycerophosphate sodium (GPS, 5 mM, 10 mM, 20 mM) and 10-9 M 1, 25-dihydroxyvitamin D3 (1, 25(OH)2D3), but was stimulated by 10-7 M 1, 25(OH)2D3 and parathyroid hormone (PTH, 10-9 M, 10-8 M, 10-7 M). Second, overexpression of FGF23 by the FGF23 adenovirus (Adv-FGF23) suppressed the formation of mineralized nodules (P < 0.001) and alkaline phosphatase (ALP) activity (P < 0.05) in both differentiated and mineralized osteoblasts. Administration of FGF receptor 3 (FGFR3) inhibitor (50 nM) was sufficient to restore the FGF23-decreased ALP activity (P < 0.05), but not for the formation of mineralized nodules. In addition, the phosphorylation of ERK increased considerably with Adv-FGF23 overexpression (P < 0.05). Administration of an ERK-specific inhibitor (10 μM) could down-regulate the phosphorylation of ERK (P-ERK) (P < 0.05) and slightly restored the Adv-FGF23-reduction of ALP activity (P=0.08). In summary, our data suggest that GPS, 1, 25(OH)2D3, and PTH could regulate FGF23 mRNA expression in vitro. FGF23 is a negative regulator of bone remodeling. FGF23 not only inhibits BMSCs osteogenesis through the FGFR3-ERK signaling pathway but also suppresses the mineralization of mature osteoblasts.