Tachysterol₂ increases the synthesis of fibroblast growth factor 23 in bone cells

Tachysterol₂ (T₂) is a photoisomer of the previtamin D₂ found in UV-B-irradiated foods such as mushrooms or baker's yeast. Due to its structural similarity to vitamin D, we hypothesized that T₂ 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 T₂ and its impact on vitamin D metabolism and Fgf23 expression. UMR106 and IDG-SW3 bone cell lines were used to elucidate the effect of T₂ on FGF23 synthesis and the corresponding mechanisms. LC-MS/MS analysis found high concentrations of T₂ in tissues and plasma of mice fed 4 vs. 0 mg/kg T₂ for 2 weeks, accompanied by a significant decrease in plasma 1,25(OH)₂D and increased renal Cyp24a1 mRNA abundance. The Fgf23 mRNA abundance in bones of mice fed T₂ was moderately higher than that in control mice. The expression of Fgf23 strongly increased in UMR106 cells treated with T₂. After Vdr silencing, the T₂ effect on Fgf23 diminished. This effect is presumably mediated by single-hydroxylated T₂-derivatives, since siRNA-mediated silencing of Cyp27a1, but not Cyp27b1, resulted in a marked reduction in T₂-induced Fgf23 gene expression. To conclude, T₂ 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 T₂ to modulate vitamin D metabolism and FGF23 synthesis raises questions about the safety of UV-B-treated foods.