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

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81 Citations (SciVal)

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)975-985
Number of pages11
JournalJournal of Cell Biology
Volume211
Issue number5
DOIs
Publication statusPublished - 7 Dec 2015

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