Regular article
Neurobiology
Expression of Bone Morphogenetic Proteins in Multiple Sclerosis Lesions

https://doi.org/10.1016/j.ajpath.2018.11.007Get rights and content
Under a Creative Commons license
open access

Bone morphogenetic proteins (BMPs) are secreted proteins that belong to the transforming growth factor-β superfamily. In the adult brain, they modulate neurogenesis, favor astrogliogenesis, and inhibit oligodendrogenesis. Because BMPs may be involved in the failure of remyelination in multiple sclerosis (MS), we characterized the expression of BMP-2, BMP-4, BMP-5, and BMP-7; BMP type II receptor (BMPRII); and phosphorylated SMAD (pSMAD) 1/5/8 in lesions of MS and other demyelinating diseases. A total of 42 MS lesions, 12 acute ischemic lesions, 8 progressive multifocal leukoencephalopathy lesions, and 10 central nervous system areas from four nonneuropathological patients were included. Lesions were histologically classified according to the inflammatory activity. The expression of BMP-2, BMP-4, BMP-5, BMP-7, BMPRII, and pSMAD1/5/8 was quantified by immunostaining, and colocalization studies were performed. In MS lesions, astrocytes, microglia/macrophages, and neurons expressed BMP-2, BMP-4, BMP-5, and BMP-7; BMPRII; and pSMAD1/5/8. Oligodendrocytes expressed BMP-2 and BMP-7 and pSMAD1/5/8. The percentage of cells that expressed BMPs, BMPRII, and pSMAD1/5/8 correlated with the inflammatory activity of MS lesions, and changes in the percentage of positive cells were more relevant in MS than in other white matter–damaging diseases. These data indicate that BMPs are increased in active MS lesions, suggesting a possible role in MS pathogenesis.

Cited by (0)

Supportedby the Fondo de Investigación Sanitaria (FIS) grant PI12/02144 (C.E.); Instituto de Salud Carlos III, Ministry of Economy, Industry and Competitivity, Spain; the Fundación Salud 2000–Merk Serono, Spain grant SERONO-2013-04 (C.E.); the Red Española de Esclerosis Múltiple grant RD12/0032 (X.M.), sponsored by the FIS; and the Ajuts per donar Suport als Grups de Recerca de Catalunya grant 2014 SGR 1082 (X.M.), sponsored by the Agència de Gestió d'Ajuts Universitaris i de Recerca, Generalitat de Catalunya, Spain.

C.C. and H.E. contributed equally to this work.

Disclosures: X.M. reports personal fees from Actelion, Bayer, Biogen, Celgene, Hoffmann-La Roche, Merck, Novartis, Oryzon Genomics, Sanofi-Genzyme, and Teva Pharmaceutical, not relevant to this work.