Fibroblast Growth Factor 23 Bone Regulation and Downstream Hormonal Activity

Mineral homeostasis of calcium and phosphate levels is one critical component to the maintenance of bone mineral density (BMD) and strength. Diseases that disrupt calcium and phosphate balanced have highlighted not only the role these minerals play in overall bone homeostasis, but also the factors, hormones and downstream transporters, responsible for mineral metabolism. The key phosphaturic hormone elucidated from studying rare heritable disorders of hypophosphatemia is Fibroblast Growth Factor 23 (FGF23). FGF23 is predominantly secreted from bone cells in an effort to maintain phosphate balance by directly controlling renal reabsorption and indirectly affecting intestinal uptake of this mineral. Multiple factors have been shown to enhance bone mRNA expression; however, FGF23 can also undergo proteolytic cleavage to control secretion of the biologically active form of the hormone. The review focuses specifically on the regulation of FGF23 and its secretion from bone as well as its hormonal actions under physiological and disease conditions.