| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,25-dihydroxyvitamin D3 up-regulates FGF23 gene expression in bone: the final link in a renal-gastrointestinal-skeletal axis that controls phosphate transport
1 Department of Pediatrics, College of Medicine, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA; Department of Orthopedic Surgery, College of Medicine, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA
2 Department of Pediatrics, College of Medicine, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA
3 Department of Orthopedic Surgery, College of Medicine, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA
4 Department of Biochemistry and Molecular Biophysics, College of Medicine, Steele Children's Research Center, University of Arizona, Tucson, AZ, USA
* To whom correspondence should be addressed. E-mail: fghishan{at}peds.arizona.edu.
Fibroblast growth factor-23 (FGF23) is a phosphaturic hormone that
decreases circulating 1
,25-dihydroxyvitamin D3 (1,25(OH)2D3) and elicits
hypophosphatemia, both of which contribute to rickets/osteomalacia. It has been
shown recently that serum FGF23 increases after treatment with the renal
1,25(OH)2D3 hormone, suggesting that 1,25(OH)2D3 negatively feedback controls
its levels by inducing FGF23. To establish the tissue of origin and the molecular
mechanism by which 1,25(OH)2D3 increases circulating FGF23, we administered
1,25(OH)2D3 to C57BL/6 mice. Within 24 hr, these mice displayed a dramatic
elevation in serum immunoreactive FGF23, and the expression of FGF23 mRNA
in bone was significantly up-regulated by 1,25(OH)2D3, but there was no effect in
several other tissues. Furthermore, we treated rat UMR-106 osteoblast-like cells
with 1,25(OH)2D3, and real-time PCR analysis revealed a dose- and time-dependent
stimulation of FGF23 mRNA concentrations. The maximum increase
in FGF23 mRNA was 1024-fold at 10-7M 1,25(OH)2D3 after 24 hr treatment, but
statistically significant differences were observed as early as 4 hr after
1,25(OH)2D3 treatment. In addition, using cotreatment with actinomycin D or
cycloheximide, we observed that 1,25(OH)2D3 regulation of FGF23 gene
expression occurs at the transcriptional level, likely via the nuclear vitamin D
receptor, and is dependent upon synthesis of an intermediary transfactor. These
results indicate that bone is a major site of FGF23 expression and source of
circulating FGF23 after 1,25(OH)2D3 administration, or physiologic up-regulation.
Our data also establish FGF23 induction by 1,25(OH)2D3 in osteoblasts as a
feedback loop between these two hormones which completes a kidney-intestine-bone
axis that mediates phosphate homeostasis.
This article has been cited by other articles:
|
|
 |
|
  B. S. Levine, C. R. Kleeman, and A. J. Felsenfeld The Journey From Vitamin D-Resistant Rickets to the Regulation of Renal Phosphate Transport Clin. J. Am. Soc. Nephrol., November 1, 2009; 4(11): 1866 - 1877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sabbagh, S. P. O'Brien, W. Song, J. H. Boulanger, A. Stockmann, C. Arbeeny, and S. C. Schiavi Intestinal Npt2b Plays a Major Role in Phosphate Absorption and Homeostasis J. Am. Soc. Nephrol., November 1, 2009; 20(11): 2348 - 2358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Masi, A. Gozzini, A. Franchi, D. Campanacci, A. Amedei, A. Falchetti, F. Franceschelli, G. Marcucci, A. Tanini, R. Capanna, et al. A Novel Recessive Mutation of Fibroblast Growth Factor-23 in Tumoral Calcinosis J. Bone Joint Surg. Am., May 1, 2009; 91(5): 1190 - 1198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Berndt and R. Kumar Novel Mechanisms in the Regulation of Phosphorus Homeostasis Physiology, February 1, 2009; 24(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Villa-Bellosta and V. Sorribas Different effects of arsenate and phosphonoformate on Pi transport adaptation in opossum kidney cells Am J Physiol Cell Physiol, January 1, 2009; 297(3): C516 - C525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Marks, L. J. Churchill, E. S. Debnam, and R. J. Unwin Matrix Extracellular Phosphoglycoprotein Inhibits Phosphate Transport J. Am. Soc. Nephrol., December 1, 2008; 19(12): 2313 - 2320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. S. Alon, R. Levy-Olomucki, W. V. Moore, J. Stubbs, S. Liu, and L. D. Quarles Calcimimetics as an Adjuvant Treatment for Familial Hypophosphatemic Rickets Clin. J. Am. Soc. Nephrol., May 1, 2008; 3(3): 658 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kawata, Y. Imanishi, K. Kobayashi, T. Miki, A. Arnold, M. Inaba, and Y. Nishizawa Parathyroid Hormone Regulates Fibroblast Growth Factor-23 in a Mouse Model of Primary Hyperparathyroidism J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2683 - 2688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liu and L. D. Quarles How Fibroblast Growth Factor 23 Works J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1637 - 1647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fyhrie, G. Gibson, and F. R.T. Nelson On the Horizon From the ORS J. Am. Acad. Ortho. Surg., April 1, 2007; 15(4): 257 - 259. [Full Text] [PDF]
|
|
|
|
|
|
S. Liu, W. Tang, J. Zhou, J. R. Stubbs, Q. Luo, M. Pi, and L. D. Quarles Fibroblast Growth Factor 23 Is a Counter-Regulatory Phosphaturic Hormone for Vitamin D J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1305 - 1315. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
