Tachysterol increases the synthesis of fibroblast growth factor 23 in bone cells.

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