Suppression of Fibroblast Growth Factor 23 in UMR106 Osteoblast-Like Cells and MC3T3-E1 Cells by Adipokine Chemerin

Abstract

Endocrine fibroblast growth factor 23 (FGF23) derived from bone governs phosphate and vitamin D metabolism. Paracrine FGF23 has additional functions in different organs. Moreover, plasma FGF23 is correlated with outcomes in chronic kidney disease. FGF23 regulation is complex depending on a plethora of different factors and conditions including AMP-dependent kinase (AMPK), inflammation, and adipokines leptin and adiponectin. Chemerin is an adipokine implicated in proinflammatory processes in adipose tissue and other organs and an activator of AMPK. Here, we investigated whether chemerin is a regulator of FGF23. UMR106 osteoblast-like cells and MC3T3-E1 osteoblasts were studied. Gene expression was assessed by qRT-PCR, FGF23 protein by ELISA, and AMPK activity by western blotting. Both cell lines expressed Cmklr1 encoding chemerin chemokine-like receptor 1. Chemerin slightly but significantly reduced Fgf23 expression. Chemerin reduced FGF23 protein abundance in the cell culture supernatant, and RNAi-mediated Cmklr1 silencing upregulated Fgf23 expression in UMR106 cells. In the presence of AMPK inhibitor compound C, chemerin failed to suppress Fgf23 in UMR106 cells. In conclusion, chemerin-dependent Cmklr1 signaling downregulates FGF23 in bone cell lines. This effect requires, at least partly, AMPK.