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

J Neuroimmunol. 2017 Sep 15:310:120-128. doi: 10.1016/j.jneuroim.2017.07.008. Epub 2017 Jul 15.

Abstract

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.

Keywords: Bone morphogenetic proteins (BMPs); Multiple sclerosis; Neural stem cells (NSCs); Neurogenesis; P19 cells.

MeSH terms

  • Adolescent
  • Adult
  • Bone Morphogenetic Protein 2 / blood*
  • Bone Morphogenetic Protein 4 / blood*
  • Bone Morphogenetic Protein 5 / blood*
  • Cytokines / blood
  • Disability Evaluation
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interferon-beta / pharmacology
  • Interferon-beta / therapeutic use
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / blood*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Oligodendroglia / metabolism
  • Signal Transduction / physiology
  • Smad Proteins / metabolism
  • Statistics as Topic
  • Young Adult

Substances

  • BMP2 protein, human
  • BMP5 protein, human
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 5
  • Cytokines
  • Smad Proteins
  • Interferon-beta