title: Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation.
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.
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK.
authors.forename: Alerie Guzman
authors.initials: AG
authors.lastname: de la Fuente
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK.
authors.forename: Oihana
authors.initials: O
authors.lastname: Errea
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: van Wijngaarden
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK.
authors.forename: Ginez A
authors.initials: GA
authors.lastname: Gonzalez
authors.affiliation: 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.
authors.forename: Christophe
authors.initials: C
authors.lastname: Kerninon
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Jarjour
authors.affiliation: AstraZeneca, Great Abington CB21 6GH, England, UK.
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Lewis
authors.affiliation: AstraZeneca, Great Abington CB21 6GH, England, UK.
authors.forename: Clare A
authors.initials: CA
authors.lastname: Jones
authors.affiliation: 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.
authors.forename: Brahim
authors.initials: B
authors.lastname: Nait-Oumesmar
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Biology, Georgetown University, Washington, DC 20057.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Huang
authors.affiliation: Medical Research Council Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: ffrench-Constant
authors.affiliation: Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 0AH, England, UK rjf1000@cam.ac.uk.
authors.forename: Robin J M
authors.initials: RJ
authors.lastname: Franklin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D009186:Myelin Sheath / Q000737:chemistry; D009836:Oligodendroglia / Q000166:cytology*; D011485:Protein Binding; D055503:Protein Multimerization; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism*; D047491:Retinoid X Receptor gamma / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D014807:Vitamin D / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; D047491:Retinoid X Receptor gamma; C579457:VDR protein, human; D014807:Vitamin D