Calcium regulates FGF-23 expression in bone

Valentin David, Bing Dai, Aline Martin, Jinsong Huang, Xiaobin Han, Leigh Quarles

Research output: Contribution to journalArticle

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Abstract

Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2-/- and Cyp27b1-/- mutant mice. Gcm2-/- mice exhibited low serum PTH and 1,25(OH)2D concentrations, hypocalcemia, and hyperphosphatemia, whereas Cyp27b1-/- mice had high PTH, undetectable 1,25(OH)2D, hypocalcemia, and hypophosphatemia. Serum FGF-23 levels were decreased in both mutant models. Doxercalciferol administration increased serum FGF-23 levels in both mutant models. PTH administration to Gcm2-/- mice also increased serum FGF-23 levels, in association with an increase in both 1,25(OH)2D and calcium concentrations. Multiple regression analysis of pooled data indicated that changes in FGF-23 were positively correlated with serum calcium and 1,25(OH)2D but not related to changes in serum phosphate concentrations. A high-calcium diet also increased serum FGF-23 concentrations in Cyp27b1-/- mice in the absence of 1,25(OH)2D and in Gcm2-/- mice with low PTH. The addition of calcium to the culture media also stimulated FGF-23 message expression in MC3T3-E1 osteoblasts. In addition, FGF-23 promoter activity in cultured osteoblasts was inhibited by the L-calcium-channel inhibitor nifedipine and stimulated by calcium ionophores. The effects of chronic low calcium to prevent 1,25(OH)2Dand PTH stimulation of FGF-23 in these mutant mouse models suggest that suppression of FGF-23 plays an important physiological adaptive response to hypocalcemia.

Original languageEnglish (US)
Pages (from-to)4469-4482
Number of pages14
JournalEndocrinology
Volume154
Issue number12
DOIs
StatePublished - Dec 1 2013

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Calcium
Bone and Bones
Serum
Hypocalcemia
Osteoblasts
fibroblast growth factor 23
Phosphates
Diet
Hyperphosphatemia
Hypophosphatemia
Calcium Ionophores
Calcitriol
Calcium Channels
Nifedipine
Vitamin D
Phosphorus
Culture Media
Regression Analysis
Hormones

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Calcium regulates FGF-23 expression in bone. / David, Valentin; Dai, Bing; Martin, Aline; Huang, Jinsong; Han, Xiaobin; Quarles, Leigh.

In: Endocrinology, Vol. 154, No. 12, 01.12.2013, p. 4469-4482.

Research output: Contribution to journalArticle

David, V, Dai, B, Martin, A, Huang, J, Han, X & Quarles, L 2013, 'Calcium regulates FGF-23 expression in bone', Endocrinology, vol. 154, no. 12, pp. 4469-4482. https://doi.org/10.1210/en.2013-1627
David, Valentin ; Dai, Bing ; Martin, Aline ; Huang, Jinsong ; Han, Xiaobin ; Quarles, Leigh. / Calcium regulates FGF-23 expression in bone. In: Endocrinology. 2013 ; Vol. 154, No. 12. pp. 4469-4482.
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