Tachysterol(2) increases the synthesis of fibroblast growth factor 23 in bone cells

Tachysterol(2) (T(2)) is a photoisomer of the previtamin D(2) found in UV-B-irradiated foods such as mushrooms or baker’s yeast. Due to its structural similarity to vitamin D, we hypothesized that T(2) can affect vitamin D metabolism and in turn, fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone that is transcriptionally regulated by the vitamin D receptor (VDR). Initially, a mouse study was conducted to investigate the bioavailability of T(2) and its impact on vitamin D metabolism and Fgf23 expression. UMR106 and IDG-SW3 bone cell lines were used to elucidate the effect of T(2) on FGF23 synthesis and the corresponding mechanisms. LC-MS/MS analysis found high concentrations of T(2) in tissues and plasma of mice fed 4 vs. 0 mg/kg T(2) for 2 weeks, accompanied by a significant decrease in plasma 1,25(OH)(2)D and increased renal Cyp24a1 mRNA abundance. The Fgf23 mRNA abundance in bones of mice fed T(2) was moderately higher than that in control mice. The expression of Fgf23 strongly increased in UMR106 cells treated with T(2). After Vdr silencing, the T(2) effect on Fgf23 diminished. This effect is presumably mediated by single-hydroxylated T(2)-derivatives, since siRNA-mediated silencing of Cyp27a1, but not Cyp27b1, resulted in a marked reduction in T(2)-induced Fgf23 gene expression. To conclude, T(2) is a potent regulator of Fgf23 synthesis in bone and activates Vdr. This effect depends, at least in part, on the action of Cyp27a1. The potential of oral T(2) to modulate vitamin D metabolism and FGF23 synthesis raises questions about the safety of UV-B-treated foods.