FGF23 and Bone and Mineral Metabolism.

FGF23 is a phosphotropic hormone produced by the bone. FGF23 works by binding to the FGF receptor-Klotho complex. Klotho is expressed in several limited tissues including the kidney and parathyroid glands. This tissue-restricted expression of Klotho is believed to determine the target organs of FGF23. FGF23 reduces serum phosphate by suppressing the expression of type 2a and 2c sodium-phosphate cotransporters in renal proximal tubules. FGF23 also decreases 1,25-dihydroxyvitamin D levels by regulating the expression of vitamin D-metabolizing enzymes, which results in reduced intestinal phosphate absorption. Excessive actions of FGF23 cause several types of hypophosphatemic rickets/osteomalacia characterized by impaired mineralization of bone matrix. In contrast, deficient actions of FGF23 result in hyperphosphatemic tumoral calcinosis with high 1,25-dihydroxyvitamin D levels. These results indicate that FGF23 is a physiological regulator of phosphate and vitamin D metabolism and indispensable for the maintenance of serum phosphate levels.