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

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

Author information

1
Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK.
2
Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK Centre for Eye Research, University of Melbourne, Royal Victorian Eye and Ear Hospital, Victoria 3002, Australia.
3
Institut du Cerveau et de la Moelle Epinière, Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1127, 75651 Paris, France.
4
Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.
5
AstraZeneca, Great Abington CB21 6GH, England, UK.
6
Department of Biology, Georgetown University, Washington, DC 20057.
7
Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK rjf1000@cam.ac.uk.

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.

PMID:
26644513
PMCID:
PMC4674280
DOI:
10.1083/jcb.201505119
[Indexed for MEDLINE]
Free PMC Article

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