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a Department of Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, USA
Key Words: Fgf-23 • phosphate regulation • vitamin D • bone
Address for correspondence: Despina Sitara, Ph.D., Department of Developmental Biology, Harvard School of Dental Medicine, REB, Room 314, 188 Longwood Avenue, Boston, MA 02115. Voice: 617-432-5749; fax: 617-432-5767. despina_sitara{at}hsdm.harvard.edu
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.
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