title: Impaired urinary osteopontin excretion in Npt2a-/- mice.
abstract: Mutations in the renal sodium-dependent phosphate cotransporters NPT2a and NPT2c have been reported in patients with renal stone disease and nephrocalcinosis. Oral phosphate supplementation is currently thought to reduce risk by reversing the hypercalciuria, but the exact mechanism remains unclear and the relative contribution of modifiers of mineralization such as osteopontin (Opn) to the formation of renal mineral deposits in renal phosphate wasting disorders has not been studied. We observed a marked decrease of renal gene expression and urinary excretion of Opn in Npt2a-/-mice, a mouse model of these disorders, at baseline. Following supplementation with phosphate Opn gene expression was restored to wild-type levels in Npt2a-/-mice; however, urine excretion of the protein remained low. To further investigate the role of Opn, we used a double-knockout strategy, which provides evidence that loss of Opn worsens the nephrocalcinosis and nephrolithiasis observed in these mice on a high-phosphate diet. These studies suggest that impaired Opn gene expression and urinary excretion in Npt2a-/-mice may be an additional risk factor for nephrolithiasis, and normalizing urine Opn levels may improve the therapy of phosphaturic disorders.
authors: Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut.
authors: Daniel
authors: D
authors: Caballero
authors: Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.|Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors: Yuwen
authors: Y
authors: Li
authors: Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut.
authors: Julian
authors: J
authors: Ponsetto
authors: Department of Infectious Diseases, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China; and.
authors: Chuanlong
authors: C
authors: Zhu
authors: Section of Endocrinology and Metabolism, Yale University School of Medicine, New Haven, Connecticut; clemens.bergwitz@yale.edu.
authors: Clemens
authors: C
authors: Bergwitz
mesh_terms: D000818:Animals; D053098:Familial Hypophosphatemic Rickets / Q000378:metabolism*; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics; D053565:Hypercalciuria / Q000378:metabolism*; D017674:Hypophosphatemia / Q000235:genetics; D007668:Kidney / Q000378:metabolism*; D008297:Male; D018345:Mice, Knockout; D009397:Nephrocalcinosis / Q000378:metabolism*; D053495:Osteopontin / Q000378:metabolism*; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000235:genetics* / Q000378:metabolism; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc / Q000235:genetics
chemical_list: C493555:Slc34a1 protein, mouse; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; D050615:Sodium-Phosphate Cotransporter Proteins, Type IIc; D053495:Osteopontin; D005346:Fibroblast Growth Factors
keywords: NPT2a; hypophosphatemia; nephrocalcinosis; osteopontin; rickets