Phosphatonins and the regulation of phosphorus homeostasis

Phosphate ions are critical for normal bone mineralization, and phosphate plays a vital role in a number of other biological processes such as signal transduction, nucleotide metabolism, and enzyme regulation. The study of rare disorders associated with renal phosphate wasting has resulted in the discovery of a number of proteins [ fibroblast growth factor 23 (FGF-23), secreted frizzled related protein 4 (sFRP-4), matrix extracellular phosphoglycoprotein, and FGF 7 (FGF-7)] that decrease renal sodium-dependent phosphate transport in vivo and in vitro. The "phosphatonins," FGF-23 and sFRP-4, also inhibit the synthesis of 1 alpha,25-dihydroxyvitamin D, leading to decreased intestinal phosphate absorption and further reduction in phosphate retention by the organism. In this review, we discuss the biological properties of these proteins, alterations in their concentrations in various clinical disorders, and their possible physiological role.