Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1992 Dec 2;119(6):1721–1728. doi: 10.1083/jcb.119.6.1721

Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen

PMCID: PMC2289768  PMID: 1469059

Abstract

Bone morphogenetic protein 2B (BMP 2B, also known as BMP 4) induces cartilage and bone morphogenesis in ectopic extraskeletal sites. BMP 2B is one of several bone morphogenetic proteins which along with activins and inhibins are members of the transforming growth factor-beta (TGF- beta) family. Both BMP 2B and activin A, but not TGF-beta 1, induce rat pheochromocytoma PC12 neuronal cell differentiation and expression of VGF, a nervous system-specific mRNA. PC12 cells exhibited approximately 2,500 receptors per cell for BMP 2B with an apparent dissociation constant of 19 pM. Extracellular matrix components, including fibronectin, laminin, and collagen type IV potentiated the activity of BMP and activin A, with the latter being the most active. Direct experiments demonstrated that radioiodinated BMP 2B bound to collagen type IV better than to either laminin or fibronectin. These data demonstrate a common neurotrophic activity of both BMP 2B and activin A, and suggest that these regulatory molecules alone and in conjunction with extracellular matrix components may play a role in both the development and repair of nervous tissue.

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aumailley M., Timpl R. Attachment of cells to basement membrane collagen type IV. J Cell Biol. 1986 Oct;103(4):1569–1575. doi: 10.1083/jcb.103.4.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baron-Van Evercooren A., Kleinman H. K., Ohno S., Marangos P., Schwartz J. P., Dubois-Dalcq M. E. Nerve growth factor, laminin, and fibronectin promote neurite growth in human fetal sensory ganglia cultures. J Neurosci Res. 1982;8(2-3):179–193. doi: 10.1002/jnr.490080208. [DOI] [PubMed] [Google Scholar]
  3. Durkin M. E., Chakravarti S., Bartos B. B., Liu S. H., Friedman R. L., Chung A. E. Amino acid sequence and domain structure of entactin. Homology with epidermal growth factor precursor and low density lipoprotein receptor. J Cell Biol. 1988 Dec;107(6 Pt 2):2749–2756. doi: 10.1083/jcb.107.6.2749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Engel J. EGF-like domains in extracellular matrix proteins: localized signals for growth and differentiation? FEBS Lett. 1989 Jul 17;251(1-2):1–7. doi: 10.1016/0014-5793(89)81417-6. [DOI] [PubMed] [Google Scholar]
  5. Folkman J., Klagsbrun M., Sasse J., Wadzinski M., Ingber D., Vlodavsky I. A heparin-binding angiogenic protein--basic fibroblast growth factor--is stored within basement membrane. Am J Pathol. 1988 Feb;130(2):393–400. [PMC free article] [PubMed] [Google Scholar]
  6. Hammonds R. G., Jr, Schwall R., Dudley A., Berkemeier L., Lai C., Lee J., Cunningham N., Reddi A. H., Wood W. I., Mason A. J. Bone-inducing activity of mature BMP-2b produced from a hybrid BMP-2a/2b precursor. Mol Endocrinol. 1991 Jan;5(1):149–155. doi: 10.1210/mend-5-1-149. [DOI] [PubMed] [Google Scholar]
  7. Herbst T. J., McCarthy J. B., Tsilibary E. C., Furcht L. T. Differential effects of laminin, intact type IV collagen, and specific domains of type IV collagen on endothelial cell adhesion and migration. J Cell Biol. 1988 Apr;106(4):1365–1373. doi: 10.1083/jcb.106.4.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kaplan D. R., Hempstead B. L., Martin-Zanca D., Chao M. V., Parada L. F. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science. 1991 Apr 26;252(5005):554–558. doi: 10.1126/science.1850549. [DOI] [PubMed] [Google Scholar]
  9. Kleinman H. K., McGarvey M. L., Liotta L. A., Robey P. G., Tryggvason K., Martin G. R. Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry. 1982 Nov 23;21(24):6188–6193. doi: 10.1021/bi00267a025. [DOI] [PubMed] [Google Scholar]
  10. Kleinman H. K., Sephel G. C., Tashiro K., Weeks B. S., Burrous B. A., Adler S. H., Yamada Y., Martin G. R. Laminin in neuronal development. Ann N Y Acad Sci. 1990;580:302–310. doi: 10.1111/j.1749-6632.1990.tb17939.x. [DOI] [PubMed] [Google Scholar]
  11. Koizumi S., Contreras M. L., Matsuda Y., Hama T., Lazarovici P., Guroff G. K-252a: a specific inhibitor of the action of nerve growth factor on PC 12 cells. J Neurosci. 1988 Feb;8(2):715–721. doi: 10.1523/JNEUROSCI.08-02-00715.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lee S. J. Identification of a novel member (GDF-1) of the transforming growth factor-beta superfamily. Mol Endocrinol. 1990 Jul;4(7):1034–1040. doi: 10.1210/mend-4-7-1034. [DOI] [PubMed] [Google Scholar]
  13. Lein P. J., Higgins D., Turner D. C., Flier L. A., Terranova V. P. The NC1 domain of type IV collagen promotes axonal growth in sympathetic neurons through interaction with the alpha 1 beta 1 integrin. J Cell Biol. 1991 Apr;113(2):417–428. doi: 10.1083/jcb.113.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Luyten F. P., Cunningham N. S., Ma S., Muthukumaran N., Hammonds R. G., Nevins W. B., Woods W. I., Reddi A. H. Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation. J Biol Chem. 1989 Aug 15;264(23):13377–13380. [PubMed] [Google Scholar]
  15. Lyons K. M., Pelton R. W., Hogan B. L. Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP-2A). Development. 1990 Aug;109(4):833–844. doi: 10.1242/dev.109.4.833. [DOI] [PubMed] [Google Scholar]
  16. Massagué J. The transforming growth factor-beta family. Annu Rev Cell Biol. 1990;6:597–641. doi: 10.1146/annurev.cb.06.110190.003121. [DOI] [PubMed] [Google Scholar]
  17. Mathews L. S., Vale W. W. Expression cloning of an activin receptor, a predicted transmembrane serine kinase. Cell. 1991 Jun 14;65(6):973–982. doi: 10.1016/0092-8674(91)90549-e. [DOI] [PubMed] [Google Scholar]
  18. Mirre C., Le Parco Y., Knibiehler B. Collagen IV is present in the developing CNS during Drosophila neurogenesis. J Neurosci Res. 1992 Jan;31(1):146–155. doi: 10.1002/jnr.490310120. [DOI] [PubMed] [Google Scholar]
  19. Ozkaynak E., Rueger D. C., Drier E. A., Corbett C., Ridge R. J., Sampath T. K., Oppermann H. OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. EMBO J. 1990 Jul;9(7):2085–2093. doi: 10.1002/j.1460-2075.1990.tb07376.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Paralkar V. M., Hammonds R. G., Reddi A. H. Identification and characterization of cellular binding proteins (receptors) for recombinant human bone morphogenetic protein 2B, an initiator of bone differentiation cascade. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3397–3401. doi: 10.1073/pnas.88.8.3397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Paralkar V. M., Nandedkar A. K., Pointer R. H., Kleinman H. K., Reddi A. H. Interaction of osteogenin, a heparin binding bone morphogenetic protein, with type IV collagen. J Biol Chem. 1990 Oct 5;265(28):17281–17284. [PubMed] [Google Scholar]
  22. Paralkar V. M., Vukicevic S., Reddi A. H. Transforming growth factor beta type 1 binds to collagen IV of basement membrane matrix: implications for development. Dev Biol. 1991 Feb;143(2):303–308. doi: 10.1016/0012-1606(91)90081-d. [DOI] [PubMed] [Google Scholar]
  23. Reddi A. H., Huggins C. Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1601–1605. doi: 10.1073/pnas.69.6.1601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schubert D., Kimura H., LaCorbiere M., Vaughan J., Karr D., Fischer W. H. Activin is a nerve cell survival molecule. Nature. 1990 Apr 26;344(6269):868–870. doi: 10.1038/344868a0. [DOI] [PubMed] [Google Scholar]
  25. Schubert D., Kimura H. Substratum-growth factor collaborations are required for the mitogenic activities of activin and FGF on embryonal carcinoma cells. J Cell Biol. 1991 Aug;114(4):841–846. doi: 10.1083/jcb.114.4.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thomsen G., Woolf T., Whitman M., Sokol S., Vaughan J., Vale W., Melton D. A. Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures. Cell. 1990 Nov 2;63(3):485–493. doi: 10.1016/0092-8674(90)90445-k. [DOI] [PubMed] [Google Scholar]
  27. Vale W., Rivier J., Vaughan J., McClintock R., Corrigan A., Woo W., Karr D., Spiess J. Purification and characterization of an FSH releasing protein from porcine ovarian follicular fluid. Nature. 1986 Jun 19;321(6072):776–779. doi: 10.1038/321776a0. [DOI] [PubMed] [Google Scholar]
  28. Vukicevic S., Luyten F. P., Reddi A. H. Stimulation of the expression of osteogenic and chondrogenic phenotypes in vitro by osteogenin. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8793–8797. doi: 10.1073/pnas.86.22.8793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Weeks B. S., DiSalvo J., Kleinman H. K. Laminin-mediated process formation in neuronal cells involves protein dephosphorylation. J Neurosci Res. 1990 Nov;27(3):418–426. doi: 10.1002/jnr.490270321. [DOI] [PubMed] [Google Scholar]
  30. Wozney J. M., Rosen V., Celeste A. J., Mitsock L. M., Whitters M. J., Kriz R. W., Hewick R. M., Wang E. A. Novel regulators of bone formation: molecular clones and activities. Science. 1988 Dec 16;242(4885):1528–1534. doi: 10.1126/science.3201241. [DOI] [PubMed] [Google Scholar]
  31. Yayon A., Klagsbrun M., Esko J. D., Leder P., Ornitz D. M. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor. Cell. 1991 Feb 22;64(4):841–848. doi: 10.1016/0092-8674(91)90512-w. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES