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

J Cell Biol. 2015 Dec 7;211(5):975-85. doi: 10.1083/jcb.201505119.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Receptors, Calcitriol
  • Retinoid X Receptor gamma
  • VDR protein, human
  • Vitamin D