1α,25-dihydroxyvitamin D3 acts predominately in mature osteoblasts under conditions of high extracellular phosphate to increase fibroblast growth factor 23 production in vitro

Osteoblasts/osteocytes are the principle sources of fibroblast growth factor 23 (FGF23), a phosphaturic hormone, but the regulation of FGF23 expression during osteoblast development remains uncertain. Because 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) and inorganic phosphate (Pi) may act as potent activators of FGF23 expression, we estimated how these molecules regulate FGF23 expression during rat osteoblast development in vitro. 1,25(OH)(2)D-3-dependent FGF23 production was restricted largely to mature cells in correlation with increased vitamin D receptor (VDR) mRNA levels, in particular, when Pi was present. Pi alone and more so in combination with 1,25(OH)(2)D-3 increased FGF23 production and VDR mRNA expression. Parathyroid hormone, stanniocalcin 1, prostaglandin E-2, FGF2, and foscarnet did not increase FGF23 mRNA expression. Thus, these results suggest that 1,25(OH)(2)D-3 may exert its largest effect on FGF23 expression/production when exposed to high levels of extracellular Pi in osteoblasts/osteocytes. Journal of Endocrinology (2010) 206, 279-286