High serum levels of BMP-2 correlate with BMP-4 and BMP-5 levels and induce reduced neuronal phenotype in patients with relapsing-remitting multiple sclerosis

•Higher sera levels of BMP-2 in patients with RR-MS•BMP-2 levels correlated with BMP-4 and -5 levels only in sera of untreated MS patients.•Sera of untreated patients inhibited the neuronal differentiation of RA-treated P19 cells.•Sera of untreated patients induced high phospho-SMAD.•A pro-neurogenic mechanism of action of IFN-β therapy.

Blockage of bone morphogenetic protein (BMP) signaling is required for differentiation of neurons and oligodendrocytes from neural stem cells (NSCs). Sera of untreated relapsing-remitting multiple sclerosis (RR-MS) patients expressed significantly higher levels of BMP-2 compared to sera of healthy controls. BMP-2 levels correlated with BMP-4 and -5 levels only in sera of untreated MS patients. Furthermore, sera of untreated patients inhibited the neuronal differentiation of RA-treated P19 cells, which was associated with induction of phospho-SMAD signaling pathway. These results suggest that BMP-2 sera levels may play a role in the failure of remyelination and neuro-regeneration in RR-MS.

Graphical abstractHigh sera levels of BMP-2 in untreated patients with RR-MS.Download high-res image (65KB)Download full-size image