Thromboxane A2 or Activated Platelets Slightly Lower Fgf23 Expression in vitro

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 pathophysiological processes in further organs, including the heart. In myocardial infarction, elevations of plasma FGF23 can be observed that may be related to left ventricular hypertrophy or fibrosis. 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 regulator of FGF23.

Experiments were performed in rat UMR-106 osteoblast-like cells and differentiated mouse MC3T3-E1 cells upon exposure to TxA2, pharmacological manipulation of TxA2 signaling, or co-incubation with platelets isolated from healthy volunteers. Fgf23 transcripts were analyzed by qRT-PCR and FGF23 protein by enzyme-linked immunosorbent assay.

As a result, TxA2 or stable TxA2 receptor agonists I-BOP or U46619 significantly suppressed Fgf23 gene expression, 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 by thrombin, but not with non-activated platelets or thrombin alone, significantly lowered Fgf23 gene expression in UMR-106 cells.

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.