Thromboxane A2 or activated platelets slightly low-er Fgf23 expression in vitro.

Abstract

Introduction: Fibroblast growth factor 23 (FGF23) has emerged as an important endocrine regulator of renal phosphate and vitamin D metabolism and as a factor implicated in patho-physiological processes in further organs including heart. In myocardial infarction, elevations of plasma FGF23 can be observed that may be related to left ventricular hypertrophy or fibro-sis. A critical event in the development of myocardial infarction and thrombosis is platelet aggregation due to thromboxane A2 (TxA2) formation. We studied whether TxA2 is a regula-tor of FGF23.

Methods: Experiments were performed in rat UMR-106 osteoblast-like cells and mouse MC3T3-E1 upon exposure to TxA2, pharmacological manipulation of TxA2 sig-naling, or co-incubation with platelets isolated from healthy volunteers. Fgf23 transcripts were analyzed by qRT-PCR and FGF23 protein by ELISA.

Results: As a result, TxA2 or stable TxA2 receptor agonists I-BOP or U46619 significantly suppressed Fgf23 gene expres-sion, an effect abrogated by TxA2 receptor antagonist SQ29548. TxA2 signaling also down-regulated FGF23 protein concentration in the cell culture supernatant. Co-incubation of UMR-106 cells with freshly isolated human thrombocytes activated with thrombin, but not with non-activated platelets or thrombin alone significantly lowered Fgf23 gene expression in UMR-106 cells.

Conclusion: Taken together, TxA2 signaling suppresses FGF23 production in UMR-106 and MC3T3-E1 bone cells. TxA2-dependent regulation of FGF23 synthesis may be particularly relevant for common diseases associated with enhanced platelet aggregation.