Keynote Address: FAM20C (DMP4), a Novel Regulator of FGF23, Plays Critical Roles in Odontogenesis and Osteogenesis

FAM20C, also known as dentin matrix protein 4 (DMP4), is a new molecule that has been studied in a limited manner. Our recent studies showed: 1) inactivation of Fam20C in mice leads to significant defects in the formation and mineralization of dentin, cementum, enamel and bone; 2) the serum phosphate level in the Fam20C-deficient mice is significantly lower, while the serum level of fibroblast growth factor 23 (FGF23) is greatly elevated; 3) the Fam20C-deficient odontoblasts, osteoblasts and ameloblasts are not full differentiated. These results (hypomineralization and hypophosphatemia) indicate that Fam20C inactivation in mice leads to hypophosphatemic rickets. We hypothesize that FAM20C promotes the differentiation of mineralized tissue-forming cells and the regulation of phosphate homeostasis via the mediation of FGF23. The defects in the hard tissues of the Fam20C-deficient mice are the cumulative result of a defect in the differentiation of mineralizing cells and a systemic consequence of hypophosphatemia.