Extracellular phosphate modulates the effect of 1α,25-dihydroxy vitamin D3 (1,25D) on osteocyte like cells

Nobuaki Ito, David M. Findlay, Paul H. Anderson, Lynda F. Bonewald, Gerald J. Atkins

Research output: Contribution to journalReview article

35 Scopus citations


1α,25-dihydroxy vitamin D3 (1,25D) is reported to up-regulate the expression of the osteocyte-derived phosphatonin, fibroblast growth factor 23 (FGF23), an effect increased by high concentrations of extracellularphosphate (Pi). Osteocytes therefore appear to sense Pi directly and this may be an importantmeans, by which FGF23 production is regulated. The intriguing possibility is that the Pi response and 1,25D pathways interact in additional ways. 1,25D also modulates the expression of other genes related to phosphate handling in cells of the osteoblast lineage. These include receptor activator of nuclear factor kappa-B ligand (RANKL) and dentin matrix acidic phosphoprotein 1 (DMP1). These cells are also capable of synthesising 1,25D due to their expression of the 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1). In this study, the mouse cell line, IDG-SW3, which differentiates into an osteocyte-like phenotype expressing Fgf23 mRNA, was utilised to address this question. Cells were differentiated for 35d and the expression level of several Pi handling or vitamin D-related genes was then evaluated in response to short-term culture with varying concentrations of extracellular Pi, in the presence or absence of 1,25D. Pi and 1,25D both increased Fgf23 mRNA expression, as well as that of N-acetylgalactosaminyltransferase 3 (Galnt3), Dmp1, phosphate-regulating gene with homologies to endopeptidases on the X chromosome (Phex), ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (Enpp1) and matrix extracellular phosphoglycoprotein (Mepe). Overall, there was a non-additive, competitive interaction between Pi and 1,25D, which was especially evident with Pi at 10 mM. Pi also modulated the 1,25D metabolic pathway, up-regulating Cyp27b1 expression and attenuating 1,25D induction of 25-hydroxyvitamin D 24-hydroxylase (Cyp24a1) mRNA. This study provides evidence that the Pi and 1,25D response in osteocytes is linked in terms of the expression of genes related to phosphate and vitamin D metabolism.

Original languageEnglish (US)
Pages (from-to)183-186
Number of pages4
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number1
StatePublished - Jan 1 2013
Externally publishedYes


  • 25D IDG-SW3 Osteocyte GALNT3
  • Phosphate FGF23 1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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