IADR Abstract Archives
High-phosphate Diet Partially Rescued FAM20C-deficient Skeleton and Tooth Defects
Objectives: Family with sequence similarity member 20C (FAM20C) is a protein kinase that phosphorylates secretory proteins, including the small-integrin-binding ligand N-linked glycoproteins (SIBLINGs), which are essential to the formation and mineralization of bone and dentin. Previously, we reported that inactivation of Fam20C in mice led to hypophosphatemic rickets/osteomalacia along with increased circulating FGF23 level and dental defects. The goal of this study was to determine whether high phosphorus diet could rescue the bone and tooth defects in the Fam20C-deficient mice.
Methods: Fam20C conditional knockout (cKO) mice were generated by crossing female Fam20C-floxed mice (Fam20Cf/f) with male Fam20Cf/+;Sox2-Cre mice. The pregnant female Fam20Cf/f mice were fed either a normal or high phosphorous (hPi) diet until the litters were weaned. The cKO and control offspring were continuously given normal or hPi diet for 4 weeks after weaning. Plain x-ray radiography, micro-CT and histology analyses were performed to evaluate the effects of hPi diet on the long bone and tooth defects in the cKO mice.
Results: Plain x-ray radiography and micro-CT radiography analyses showed that the hPi diet improved the shape and density of the Fam20C-deficient femurs/tibiae, and rescued the growth plate defects in the long bone. Histology analyses further demonstrated that hPi diet completely rescued the growth plate-widening defects in the long bone and restored the expanded zone of the hypertrophic chondrocytes to the normal width. In addition, the hPi diet partially rescued the dental defects (including defects of dentin, cementum and pulp chamber) and alveolar bone defects in the cKO mice.
Conclusions: These results suggested that the high phosphate diet significantly improved the skeletal and dental defects of the Fam20C-deficient mice, implying that hypophosphatemia played a crucial pathogenic role in the development of the skeletal and dental abnormalities in Fam20C-deficient subjects.
Methods: Fam20C conditional knockout (cKO) mice were generated by crossing female Fam20C-floxed mice (Fam20Cf/f) with male Fam20Cf/+;Sox2-Cre mice. The pregnant female Fam20Cf/f mice were fed either a normal or high phosphorous (hPi) diet until the litters were weaned. The cKO and control offspring were continuously given normal or hPi diet for 4 weeks after weaning. Plain x-ray radiography, micro-CT and histology analyses were performed to evaluate the effects of hPi diet on the long bone and tooth defects in the cKO mice.
Results: Plain x-ray radiography and micro-CT radiography analyses showed that the hPi diet improved the shape and density of the Fam20C-deficient femurs/tibiae, and rescued the growth plate defects in the long bone. Histology analyses further demonstrated that hPi diet completely rescued the growth plate-widening defects in the long bone and restored the expanded zone of the hypertrophic chondrocytes to the normal width. In addition, the hPi diet partially rescued the dental defects (including defects of dentin, cementum and pulp chamber) and alveolar bone defects in the cKO mice.
Conclusions: These results suggested that the high phosphate diet significantly improved the skeletal and dental defects of the Fam20C-deficient mice, implying that hypophosphatemia played a crucial pathogenic role in the development of the skeletal and dental abnormalities in Fam20C-deficient subjects.