TY - JOUR
T1 - Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation
AU - de la Fuente, Alerie Guzman
AU - Errea, Oihana
AU - van Wijngaarden, Peter
AU - Gonzalez, Ginez A.
AU - Kerninon, Christophe
AU - Jarjour, Andrew A.
AU - Lewis, Hilary J.
AU - Jones, Clare A.
AU - Nait-Oumesmar, Brahim
AU - Zhao, Chao
AU - Huang, Jeffrey K.
AU - ffrench-Constant, Charles
AU - Franklin, Robin J. M.
PY - 2015/12/7
Y1 - 2015/12/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84958742614&partnerID=8YFLogxK
U2 - 10.1083/jcb.201505119
DO - 10.1083/jcb.201505119
M3 - Article
C2 - 26644513
AN - SCOPUS:84958742614
VL - 211
SP - 975
EP - 985
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 5
ER -