RXR-VDR regulates OPC differentiation

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.This work was supported by the United Kingdom Multiple Sclerosis Society, the Wellcome Trust, Sir David and Isobel Walker Trust, the Medical Research Council, “Investissements d’avenir” Instituts Hospitalo-Universitaires A Institut du Cerveau et de la Moelle Epiniere, a National Health and Medical Research Council Early Career Fellowship (grant 628928), and Obra Social “La Caixa.