de la Fuente et al. reveal how the vitamin D receptor (VDR) promotes the differentiation of oligodendrocyte progenitor cells (OPCs), thereby boosting myelin sheath regeneration.
When central nervous system axons lose their insulating myelin sheath—due, for example, to demyelinating diseases such as multiple sclerosis (MS)—OPCs migrate toward the damage and differentiate into mature, myelin-producing oligodendrocytes. The nuclear receptor retinoid X receptor γ (RXR-γ) promotes OPC differentiation and remyelination, but nuclear receptors generally function as heterodimers, so de la Fuente et al. set out to identify RXR-γ’s binding partners.
RXR-γ bound to several nuclear receptors, including VDR, in OPCs and mature oligodendrocytes. Inhibiting VDR signaling impaired OPC differentiation and reduced the cells’ ability to remyelinate axons ex vivo. Vitamin D, in contrast, boosted OPC differentiation.
Low vitamin D levels have been linked to the onset of MS, and de la Fuente et al.’s findings suggest that the vitamin might also affect the disease’s progression by controlling myelin sheath regeneration, a process that declines with age. VDR agonists might therefore be able to enhance remyelination in MS patients. Indeed, the researchers found that VDR was expressed in OPCs and oligodendrocytes present in MS brain lesions.
The team now wants to identify which genes are downstream targets of the RXR-γ–VDR heterodimer. They also want to investigate whether other partners of RXR-γ also play a role in OPC differentiation and remyelination.
Text by Ben Short