title: Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D.
abstract: The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is not well understood. It was found that administration of 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) to mice rapidly increased serum FGF23 concentrations from a basal level of 90.6 +/- 8.1 to 213.8 +/- 14.6 pg/ml at 8 h (mean +/- SEM; P < 0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked hypophosphatemic rickets, administration of 1,25(OH)(2)D(3) further increased circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH)(2)D(3) levels were associated with a three-fold reduction in FGF23 levels that were increased by administration of 1,25(OH)(2)D(3). In osteoblast cell cultures, 1,25(OH)(2)D(3) but not calcium, phosphate, or parathyroid hormone stimulated FGF23 mRNA levels and resulted in a dose-dependent increase in FGF23 promoter activity. Overexpression of a dominant negative vitamin D receptor inhibited 1,25(OH)(2)D(3) stimulation of FGF23 promoter activity, and mutagenesis of the FGF23 promoter identified a vitamin D-responsive element (-1180 GGAACTcagTAACCT -1156) that is responsible for the vitamin D effects. These data suggest that 1,25(OH)(2)D(3) is an important regulator of FGF23 production by osteoblasts in bone. The physiologic role of FGF23 may be to act as a counterregulatory phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.
authors.affiliation: Department of Internal Medicine and the Kidney Institute, University of Kansas Medical Center, 3901 Rainbow Boulevard, Room 6020 WHE, MS 3018, Kansas City, KS 66160, USA. sliu@kumc.edu
authors.forename: Shiguang
authors.initials: S
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Tang
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Jason R
authors.initials: JR
authors.lastname: Stubbs
authors.forename: Qiang
authors.initials: Q
authors.lastname: Luo
authors.forename: Min
authors.initials: M
authors.lastname: Pi
authors.forename: L Darryl
authors.initials: LD
authors.lastname: Quarles
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology; D017674:Hypophosphatemia / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*
chemical_list: C000717428:Fgf23 protein, mouse; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002117:Calcitriol