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Calcium regulates FGF-23 expression in bone.

Valentin David1, Bing Dai, Aline Martin

  • 1MD, Coleman College of Medicine Building, Suite B226, University of Tennessee Health Science Center, 956 Court Avenue, Memphis Tennessee 38163. dquarles@uthsc.edu.

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Summary
This summary is machine-generated.

Calcium directly regulates fibroblast growth factor 23 (FGF-23) production. This study shows FGF-23 levels increase with calcium, independent of phosphate or vitamin D, suggesting calcium

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Area of Science:

  • Endocrinology
  • Mineral Metabolism
  • Molecular Biology

Background:

  • Fibroblast growth factor 23 (FGF-23) is a key hormone regulating phosphate and vitamin D metabolism.
  • Calcium's role in FGF-23 regulation is not fully understood, particularly its interplay with phosphorus, 1,25-dihydroxyvitamin D [1,25(OH)2D], and parathyroid hormone (PTH).

Purpose of the Study:

  • To investigate the regulation of FGF-23 by calcium, phosphorus, 1,25(OH)2D, and PTH.
  • To examine FGF-23 expression in genetic mouse models with altered mineral metabolism.

Main Methods:

  • Utilized Gcm2(-/-) and Cyp27b1(-/-) mutant mice with distinct mineral profiles.
  • Administered PTH, doxercalciferol, and high-calcium diets to assess FGF-23 responses.
  • Analyzed FGF-23 expression in MC3T3-E1 osteoblasts under varying calcium conditions and with pharmacological agents.

Main Results:

  • Serum FGF-23 levels were decreased in both Gcm2(-/-) and Cyp27b1(-/-) mutant mice.
  • FGF-23 levels increased with doxercalciferol and PTH administration in relevant models.
  • Multiple regression analysis revealed a positive correlation between FGF-23 and serum calcium and 1,25(OH)2D, but not phosphate.
  • High-calcium diet, calcium ionophores, and direct calcium addition stimulated FGF-23 expression in vivo and in vitro.
  • Calcium channel inhibition reduced FGF-23 promoter activity.

Conclusions:

  • Calcium is a direct stimulator of FGF-23 production in osteoblasts.
  • FGF-23 regulation is primarily influenced by serum calcium and 1,25(OH)2D levels.
  • Suppression of FGF-23 in hypocalcemia represents a physiological adaptation.