Correlation among hyperphosphatemia, type II sodium phosphate transporter activity, and vitamin D metabolism in Fgf-23 null mice.

Phosphate homeostasis is mostly regulated through humoral factors exerting direct or indirect effects on transporter proteins located in the intestine and kidney. Fibroblast growth factor 23 (FGF-23) is a major phosphate-regulating molecule, which can affect both renal and intestinal phosphate uptake to influence overall mineral ion homeostasis. We have found that Fgf-23 gene knockout mice (Fgf-23(-/-)) develop hyperphosphatemia that consequently leads to abnormal bone mineralization, and severe soft tissue calcifications. On the contrary, FGF-23 transgenic mice develop hypophosphatemia and produce rickets-like features in the mutant bone. Further studies using our Fgf-23(-/-) mice have identified an inverse correlation between Fgf-23, and vitamin D or NaPi2a; genomic elimination of either vitamin D or NaPi2a activities from Fgf-23(-/-) mice could reverse severe hyperphosphatemia to hypophosphatemia, and consequently could alter skeletal mineralization, suggesting that regulation of phosphate homeostasis in Fgf-23(-/-) mice is vitamin D- and NaPi2a-mediated process.