Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation

Alerie Guzman de la Fuente, Oihana Errea, Peter van Wijngaarden, Ginez A Gonzalez, Christophe Kerninon, Andrew A Jarjour, Hilary J Lewis, Clare A Jones, Brahim Nait-Oumesmar, Chao Zhao, Jeffrey K Huang, Charles ffrench-Constant, Robin J M Franklin

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

The mechanisms regulating differentiation of oligodendrocyte (OLG) progenitor cells (OPCs) into mature OLGs are key to understanding myelination and remyelination. Signaling via the retinoid X receptor γ (RXR-γ) has been shown to be a positive regulator of OPC differentiation. However, the nuclear receptor (NR) binding partner of RXR-γ has not been established. In this study we show that RXR-γ binds to several NRs in OPCs and OLGs, one of which is vitamin D receptor (VDR). Using pharmacological and knockdown approaches we show that RXR-VDR signaling induces OPC differentiation and that VDR agonist vitamin D enhances OPC differentiation. We also show expression of VDR in OLG lineage cells in multiple sclerosis. Our data reveal a role for vitamin D in the regenerative component of demyelinating disease and identify a new target for remyelination medicines.

Original languageEnglish
Pages (from-to)975-85
JournalThe Journal of cell biology
Volume211
Issue number5
DOIs
Publication statusPublished - 07 Dec 2015
Externally publishedYes

Bibliographical note

© 2015 de la Fuente et al.

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis/metabolism
  • Myelin Sheath/chemistry
  • Oligodendroglia/cytology
  • Protein Binding
  • Protein Multimerization
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcitriol/metabolism
  • Retinoid X Receptor gamma/metabolism
  • Signal Transduction
  • Stem Cells/cytology
  • Vitamin D/metabolism

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