title: PTH ablation ameliorates the anomalies of Fgf23-deficient mice by suppressing the elevated vitamin D and calcium levels.
abstract: Fibroblast growth factor 23 (FGF23) is a key regulator of mineral ion homeostasis. Genetic ablation of Fgf23 in mice leads to severe biochemical disorders including elevated serum 1,25-dihydroxyvitamin D [1,25(OH)2D], hypercalcemia, hyperphosphatemia, and marked decreased PTH levels. Because PTH stimulates 1,25(OH)2D production and increases serum calcium levels, we hypothesized that ablation of PTH from the Fgf23 knockout (Fgf23-/-) mice could suppress these affects, thus ameliorating the soft tissue and skeletal anomalies in these animals. In this study, we generated a genetic mouse model with dual ablation of the Fgf23/PTH genes. The data show that deletion of PTH does suppress the markedly higher serum 1,25(OH)2D and calcium levels observed in Fgf23-/- mice and results in much larger, heavier, and more active double-knockout mice with improved soft tissue and skeletal phenotypes. On the contrary, when we infused PTH (1-34) peptide into Fgf23-/- mice using osmotic minipumps, serum 1,25(OH)2D and calcium levels were increased even further, leading to marked reduction in trabecular bone. These results indicate that PTH is able to modulate the anomalies of Fgf23-/- mice by controlling serum 1,25(OH)2D and calcium levels.
authors: Department of Developmental Biology, Harvard School of Dental Medicine, Research and Education Building, Room 303, 188 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors: Quan
authors: Q
authors: Yuan
authors: Despina
authors: D
authors: Sitara
authors: Tadatoshi
authors: T
authors: Sato
authors: Michael
authors: M
authors: Densmore
authors: Hiroaki
authors: H
authors: Saito
authors: Christine
authors: C
authors: Schüler
authors: Reinhold G
authors: RG
authors: Erben
authors: Beate
authors: B
authors: Lanske
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D007260:Infusion Pumps; D051379:Mice; D018345:Mice, Knockout; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014807:Vitamin D / Q000097:blood*
chemical_list: C000717428:Fgf23 protein, mouse; D010281:Parathyroid Hormone; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002118:Calcium