New concepts in regulation and function of the FGF23

In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.