Recombinant Human FGF-23

Fibroblast growth factor-23 (FGF-23), also known as ADHR and HYPF, is a secreted, non-glycosylated protein and member of the FGF family. The FGF family plays a central role during prenatal development and postnatal growth and regeneration of a variety of tissues, by promoting cellular proliferation and differentiation (1). FGF-23 is mostly expressed in bone and connective tissue and exerts its effects through a ternary complex that includes Klotho and an FGF receptor (FGF R4 or the “c” isoforms of FGF R1 or FGF R3); however, Klotho has a restricted distribution that limits FGF-23 activity (2). This complex is an essential regulator of the renal sodium phosphate co-transporter which is accomplished by modulating SLC34A1 levels (3). FGF-23 also inhibits 1-hydroxylase which is responsible for the conversion of calcifediol to calcitriol (the biologically active form of Vitamin D) (4). It up-regulates EGR1 expression in the presence of KL and acts directly on the parathyroid to decrease PTH secretion. Additionally, FGF-23 negatively regulates osteoblast differentiation and matrix mineralization. FGF-23 was identified by its mutations associated with autosomal dominant hypophosphatemic rickets (ADHR), an inherited phosphate wasting disorder (5). Abnormally high level expression of FGF-23 was found in oncogenic hypophosphatemic osteomalacia (OHO), a phenotypically similar disease caused by abnormal phosphate metabolism (6). Mutations in this gene have also been shown to cause familial tumoral calcinosis with hyperphosphatemia.