Oligodendroglial lineage cells express nuclear p57kip2 in multiple sclerosis lesions

Glia. 2013 Aug;61(8):1250-60. doi: 10.1002/glia.22512. Epub 2013 Jul 5.


Impaired remyelination in multiple sclerosis (MS) might be due to the failure of oligodendrocyte precursor cells (OPC) to differentiate into myelinating oligodendrocytes. Animal experimental data have shown that p57kip2 inhibits oligodendroglial differentiation, indicating that this factor could contribute to remyelination failure. This study investigates oligodendroglial p57kip2 expression and its association with remyelination in MS lesions. To analyze the potential association of p57kip2 expression with human oligodendroglial maturation, double immunofluorescence staining was performed on brain tissue from 30 MS patients and 20 controls. Anti-p57kip2 antibody was combined with either anti-Nogo-A to label mature oligodendrocytes or anti-Olig2 antibodies to identify immature OPCs. We evaluated MS lesions with or without remyelination, the periplaque white matter (PPWM) as well as control white matter (WM). p57kip2-expressing cells were assessed and correlated with the extent of remyelination. Most Nogo-A-positive oligodendrocytes (range, 87-98%) and all Olig2strong-positive OPCs expressed p57kip2 in MS lesions, in the PPWM and in control WM. p57kip2 expression in oligodendrocytes and OPCs were similar in MS lesions with remyelination compared to MS lesions lacking remyelination. Interestingly, all oligodendroglial lineage cells showed nuclear p57kip2 expression only, with mature oligodendrocytes expressing p57kip2 at low or intermediate levels and OPCs featuring strong expression levels, indicating that this factor may be dynamically expressed during maturation processes. Therefore, p57kip2 appears to be widely expressed in the human oligodendroglial lineage, and potential beneficial effects on remyelination in the MS brain are not based on subcellular p57kip2 localization shifts, as suggested by previous animal experiments.

Keywords: MS; oligodendrocyte precursor cells; oligodendrocytes; p57kip2; remyelination.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Lineage / genetics
  • Child
  • Child, Preschool
  • Cyclin-Dependent Kinase Inhibitor p57 / biosynthesis*
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics
  • Female
  • Gene Expression Regulation*
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / metabolism*
  • Multiple Sclerosis / pathology*
  • Myelin Sheath / genetics
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology
  • Oligodendroglia / metabolism*
  • Oligodendroglia / pathology*
  • Subcellular Fractions / metabolism
  • Subcellular Fractions / pathology
  • Young Adult


  • Cyclin-Dependent Kinase Inhibitor p57