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

doi:10.1083/jcb.201505119

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

Research output: Contribution to journal › Article › peer-review

109 Citations (Scopus)

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 language	English
Pages (from-to)	975-85
Journal	The Journal of cell biology
Volume	211
Issue number	5
DOIs	https://doi.org/10.1083/jcb.201505119
Publication status	Published - 07 Dec 2015
Externally published	Yes

Bibliographical note

Keywords

Adult
Aged
Aged, 80 and over
Animals
Cell Differentiation
Cell Lineage
Female
Gene Expression Regulation
Humans
Male
Middle Aged
Multiple Sclerosis/metabolism
Myelin Sheath/chemistry
Oligodendroglia/cytology
Protein Binding
Protein Multimerization
Rats
Rats, Sprague-Dawley
Receptors, Calcitriol/metabolism
Retinoid X Receptor gamma/metabolism
Signal Transduction
Stem Cells/cytology
Vitamin D/metabolism

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de la Fuente, A. G., Errea, O., van Wijngaarden, P., Gonzalez, G. A., Kerninon, C., Jarjour, A. A., Lewis, H. J., Jones, C. A., Nait-Oumesmar, B., Zhao, C., Huang, J. K., ffrench-Constant, C., & Franklin, R. J. M. (2015). Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation. The Journal of cell biology, 211(5), 975-85. https://doi.org/10.1083/jcb.201505119

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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. ",

keywords = "Adult, Aged, Aged, 80 and over, Animals, Cell Differentiation, Cell Lineage, Female, Gene Expression Regulation, Humans, Male, Middle Aged, Multiple Sclerosis/metabolism, Myelin Sheath/chemistry, Oligodendroglia/cytology, Protein Binding, Protein Multimerization, Rats, Rats, Sprague-Dawley, Receptors, Calcitriol/metabolism, Retinoid X Receptor gamma/metabolism, Signal Transduction, Stem Cells/cytology, Vitamin D/metabolism",

author = "{de la Fuente}, {Alerie Guzman} and Oihana Errea and {van Wijngaarden}, Peter and Gonzalez, {Ginez A} and Christophe Kerninon and Jarjour, {Andrew A} and Lewis, {Hilary J} and Jones, {Clare A} and Brahim Nait-Oumesmar and Chao Zhao and Huang, {Jeffrey K} and Charles ffrench-Constant and Franklin, {Robin J M}",

note = "{\textcopyright} 2015 de la Fuente et al.",

year = "2015",

month = dec,

day = "7",

doi = "10.1083/jcb.201505119",

language = "English",

volume = "211",

pages = "975--85",

journal = "The Journal of cell biology",

issn = "0021-9525",

publisher = "Rockefeller University Press",

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de la Fuente, AG, Errea, O, van Wijngaarden, P, Gonzalez, GA, Kerninon, C, Jarjour, AA, Lewis, HJ, Jones, CA, Nait-Oumesmar, B, Zhao, C, Huang, JK, ffrench-Constant, C & Franklin, RJM 2015, 'Vitamin D receptor-retinoid X receptor heterodimer signaling regulates oligodendrocyte progenitor cell differentiation', The Journal of cell biology, vol. 211, no. 5, pp. 975-85. https://doi.org/10.1083/jcb.201505119

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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Animals

KW - Cell Differentiation

KW - Cell Lineage

KW - Female

KW - Gene Expression Regulation

KW - Humans

KW - Male

KW - Middle Aged

KW - Multiple Sclerosis/metabolism

KW - Myelin Sheath/chemistry

KW - Oligodendroglia/cytology

KW - Protein Binding

KW - Protein Multimerization

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Calcitriol/metabolism

KW - Retinoid X Receptor gamma/metabolism

KW - Signal Transduction

KW - Stem Cells/cytology

KW - Vitamin D/metabolism

U2 - 10.1083/jcb.201505119

DO - 10.1083/jcb.201505119

M3 - Article

C2 - 26644513

SN - 0021-9525

VL - 211

SP - 975

EP - 985

JO - The Journal of cell biology

JF - The Journal of cell biology

IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

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