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

Autor: Ewendt F; Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany., Kotwan J; Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.; NutriCARD Competence Cluster for Nutrition and Cardiovascular Health, Halle (Saale), Germany., Ploch S; Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany., Feger M; Department of Physiology, University of Hohenheim, Stuttgart, Germany., Hirche F; Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany., Föller M; Department of Physiology, University of Hohenheim, Stuttgart, Germany., Stangl GI; Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.; NutriCARD Competence Cluster for Nutrition and Cardiovascular Health, Halle (Saale), Germany.
Jazyk: angličtina
Zdroj: Frontiers in nutrition [Front Nutr] 2022 Jul 25; Vol. 9, pp. 948264. Date of Electronic Publication: 2022 Jul 25 (Print Publication: 2022).
DOI: 10.3389/fnut.2022.948264
Abstrakt: 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Ewendt, Kotwan, Ploch, Feger, Hirche, Föller and Stangl.)
Databáze: MEDLINE