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“Introduction Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone produced primarily by osteocytes

[1]. FGF23 expression is predominantly regulated by plasma phosphate (P) [2] and 1,25-dihydroxyvitamin D (1,25-(OH)2D) [3]. The principal target organ of FGF23 is the kidney where it causes the internalization of sodium–phosphate cotransporters in renal tubular cells and the suppression of 1α-hydroxylase activity [4], thus decreasing plasma P by increasing urinary phosphate excretion and down-regulating 1,25-(OH)2D concentrations, respectively. The FGF23 gene encodes the 251 amino acid FGF23 peptide, which includes a signal peptide (SP) of 24 amino acids. Prior to secretion the SP is cleaved to form the intact FGF23 protein. The intact FGF23 protein contains the arginine–X–X–arginine (RXXR) motif which is a protease recognition site [5]. When proteolytically cleaved between Arg179 and Ser180 the intact

LOXO-101 mouse FGF23 (~32 kDa) forms an N- and C-terminal (~12 kDa) fragment (Fig. 1). It is thought that only the intact FGF23 protein is biologically functional and that the cleavage step forming the N- and C-terminal fragments renders the protein inactive [6]. Fig. 1 Schematic of the FGF23 protein starting with the full FGF23 product (251 amino acids), the signal peptide (24 amino acids) is then cleaved off to produce the intact FGF23 hormone which is considered biologically active. Proteolytic cleavage then occurs at the end CYTH4 of the RXXR motif between R179 and S180 to produce the biologically inactive N- and C-terminal fragments. Both the intact hormone and the C-terminal fragments are recognized by the C-terminal Immutopics ELISA assay [8] There are currently two commercially available enzyme-linked immunosorbent assays (ELISA) for measurement of FGF23 concentration, namely the Kainos Intact FGF23 ELISA (Kainos Laboratories, Inc., Tokyo, Japan) and the Immutopics C-terminal FGF23 ELISA (Immutopics, Inc., CA, USA). The Intact ELISA uses two antibodies that recognize the Selleckchem BI-6727 N-terminal and C-terminal regions and therefore only recognizes the full, intact FGF23 hormone prior to proteolytic cleavage. However, the two antibodies used in the C-terminal ELISA detect epitopes within the C-terminal region and therefore recognizes both the intact hormone and the C-terminal fragment.