Expression of Bone Morphogenetic Proteins In Multiple Sclerosis Lesions.

Bone morphogenetic proteins (BMPs) are secreted proteins that belong to the transforming growth factor-beta superfamily. In the adult brain, they modulate neurogenesis, favor astrogliogenesis, and inhibit oligodendrogenesis. As BMPs may be involved in the failure of remyelination in multiple sclerosis (MS), we characterized the expression of BMP-2, -4, -5, and -7; BMP type II receptor (BMPRII); and phosphorylated (p)SMAD 1/5/8 in lesions of MS and other demyelinating diseases. Forty-two MS lesions, 12 acute ischemic lesions, eight progressive multifocal leucoencephalopathy lesions, and 10 CNS areas from four non-neuropathological 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, -4, -5, and -7; BMPRII; and pSMAD1/5/8, whereas oligodendrocytes expressed BMP-2 and -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.