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Detection of two transforming growth factor-β-related morphogens, bone morphogenetic proteins-4 and-5, in RNA of multiple sclerosis and Creutzfeldt-Jakob disease lesions

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Abstract

The bone morphogenetic proteins (BMPs) constitute a novel subfamily of the transforming growth factor type β (TGF-β) supergene family. Here we demonstrate, using polymerase chain reaction (PCR) BMP-4 and BMP-5 messages in RNA isolated from multiple sclerosis (MS) plaque tissue. This is the first demonstration of BMP expression in an inflammatory lesion in general, and in MS in particular. However, BMP-4 and BMP-5 messages could be detected in RNA isolated from a Morbus Creutzfeldt-Jakob (CJD) lesion. Even in normal brain, RNA expression of BMP-4, but not that of BMP-5, was detected. Therefore, BMP-5 gene expression seems to be associated with MS and CJD lesions, whereas the BMP-4 gene appears to be constitutively expressed in the human brain. As TGF-βs and BMPs are regulators of regenerative processes and contribute to regulation of chemoattraction and local immunoreactivity, BMP-4 and BMP-5 might be involved in aspects of MS lesion formation unknown so far. PCR analysis of human cell lines demonstrate BMP-4 and BMP-5 expression in leukocytic cells, suggesting that infiltrating leukocytes contribute at least in part to BMP-4 and BMP-5 mRNAs of the MS plaque.

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References

  1. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA (1988) Novel regulators of bone formation: molecular clones and activities. Science 242:1528–1543

    Google Scholar 

  2. Wozney JM (1992) The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev 32:160–167

    Google Scholar 

  3. Rosen V, Thies RS (1992) The BMP proteins in bone formation and repair. Trends Genet 8:97–102

    Google Scholar 

  4. Lyons KM, Pelton RW, Hogan BLM (1989b) Patterns of expression of murine vgr-1 and BMP-2a suggest that transforming growth factor-β-like genes coordinately regulate aspects of embryonic development. Genes Dev 3:1657–1668

    Google Scholar 

  5. Jones CM, Lyons KM, Hogan BLM (1991) Involvement of bone morphogenetic protein-4 (BMP-4) and vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111:531–542

    Google Scholar 

  6. Bryant PJ (1988) Localized cell death caused by mutations in a Drosophila gene coding for a transforming growth factor-β homolog. Dev Biol 128:386–395

    Google Scholar 

  7. Paralkar VM, Weeks BS, Yu YM, Kleinman HK, Reddi AH (1992) Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen. J Cell Biol 119:1721–1728

    Google Scholar 

  8. Perides G, Safran RM, Rueger DC, Charness ME (1992) Induction of the neural cell adhesion molecule and neuronal aggregation by osteogenic protein 1. Proc Natl Acad Sci USA 89:10326–10330

    Google Scholar 

  9. Sheppard AM, Hamilton SK, Pearlman AL (1991) Changes in the distribution of extracellular matrix components accompany early morphogenetic events in mammalian cortical development. J Neurosci 11:3928–3942

    Google Scholar 

  10. Schluesener HJ, Meyermann R (1993) Intercrines in brain pathology. Expression of intercrines in a multiple sclerosis and Morbus Creutzfeldt-Jakob lesion. Acta Neuropathol 86:393–396

    Google Scholar 

  11. Schluesener HJ, Koeppel C, Jung S (1992) Multidrug transport in human autoimmune T line cells and peripheral blood lymphocytes. Immunopharmacology 23:37–48

    Google Scholar 

  12. Schluesener HJ, Meyermann R (1991) Spontaneous multidrug transport in human glioma cells is regulated by transforming growth factors type-β. Acta Neuropathol 81:641–648

    Google Scholar 

  13. Bentley H, Hamdy C, Hart A, Seid M, Williams L, Johnstone D, Russell RG (1992) Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. Br J Cancer 66:1159–1163

    Google Scholar 

  14. Flanders KC, Lüdecke G, Engels S, Cissel DS, Roberts AB, Kondaiah P, Lafyatis R, Sporn MB, Unsicker K (1991) Localization and actions of transforming growth factors-β in the embryonic nervous system. Development 113:183–191

    Google Scholar 

  15. Schluesener HJ, Meyermann R (1991b) 78-1, 78-2, 78-3 and the bone morphogenetic protein BMP2: members of the transforming growth factor type β supergene family with different morphogenetic effects on rat astrocyte cultures. Autoimmunity 9:77–81

    Google Scholar 

  16. Johnson MD, Jennings MT, Gold LI, Moses HL (1993) Transforming growth factor-beta in neural embryogenesis and neoplasia. Hum Pathol 24:457–462

    Google Scholar 

  17. Cunningham NS, Paralkar V, Reddi AH (1992) Osteogenin and recombinant bone morphogenetic protein 2B are chemotactic for human monocytes and stimulate transforming growth factor beta 1 mRNA expression. Proc Natl Acad Sci USA 89:11740–11744

    Google Scholar 

  18. Finch CE, Laping NJ, Morgan TE, Nichols NR, Pasinetti GM (1993) 79-1 is an organizer of responses of neurodegeneration. J Cell Biochem 53:314–322

    Google Scholar 

  19. Perides G, Safran RM, Downing LA, Charness ME (1994) Regulation of neural cell adhesion molecule and L1 by the transforming growth factor-beta superfamily. Selective effects of the bone morphogenetic proteins. J Biol Chem 269:765–770

    Google Scholar 

  20. Burt DW, Law AS (1994) Evolution of the transforming growth factor-beta superfamily. Prog Growth Factor Res 5:99–118

    Google Scholar 

  21. Graham A, Francis-West P, Brickell P, Lumsden A (1994) The signalling molecule BMP4 mediates apoptosis in the rhombencephalic neural crest. Nature 372:684–686

    Google Scholar 

  22. D'Allessandro JS, Yetz-Aldape J, Wang E (1994) Bone morphogenetic proteins induce differentiation in astrocyte lineage cells. Growth Factors 11:53–69

    Google Scholar 

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Deininger, M., Meyermann, R. & Schluesener, H. Detection of two transforming growth factor-β-related morphogens, bone morphogenetic proteins-4 and-5, in RNA of multiple sclerosis and Creutzfeldt-Jakob disease lesions. Acta Neuropathol 90, 76–79 (1995). https://doi.org/10.1007/BF00294462

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  • DOI: https://doi.org/10.1007/BF00294462

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