FAM20C may mediate phosphate homeostasis via FGF23.

<p>FAM20C, DMP1 and PHEX may share similar mechanisms in their involvement in the bone-kidney axis when regulating phosphate homeostasis via FGF23. FAM20C secreted by osteoblasts/osteocytes may regulate the phosphaturic hormone FGF23 expression in these cells. FGF23 targets the Klotho/FGF receptor (FGFR) complexes in the kidney, reducing the expression of the renal sodium-phosphate cotransporters NaPi-2a/2c in the proximal tubules, thereby accelerates phosphate excretion into the urine and helps maintaining the serum phosphate levels in the normal range. While inactivation of FAM20C led to remarkable reduction of DMP1 in the mice and osteogenic cell lines, and recombinant FAM20C significantly increased the expression of DMP1 in MC3T3-E1 cells, it is unclear if FAM20C regulates FGF23 and phosphate homeostasis <i>via</i> DMP1 (dotted arrow) or FAM20C directly regulates FGF23 (dashed line).