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Gene Review

BMP4  -  bone morphogenetic protein 4

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Disease relevance of BMP4


High impact information on BMP4


Biological context of BMP4


Anatomical context of BMP4

  • It is concluded that a BMP-signaling system, consisting of BMP2, BMP4, type II and I receptors, is present in bovine antral follicles and that this system plays a role in development and functioning of these follicles rather than in final oocyte maturation and cumulus expansion [5].
  • The immunostaining of BMP2 and BMP4 was limited to theca interna and approximately 25% of oocytes of antral follicles [5].
  • Exogenously added BMP2 or BMP4 to IVM medium did not affect oocyte nuclear maturation, cumulus cell expansion, nor blastocyst formation following IVF [5].
  • In mice with inherited photoreceptor degeneration, there was a dramatic decrease in BMP4 mRNA in retina and RPE during and after the degeneration. mRNA for the type II BMP receptor was observed in freshly isolated and cultured RPE cells, isolated retina, and freshly isolated bovine aortic endothelial cells [6].
  • The same cells express at least two potential ligands for these receptors (BMP-4 and -7), whereas bovine granulosa cells and oocytes express BMP-6 [7].

Associations of BMP4 with chemical compounds

  • Thymidine incorporation in early-passage RPE cells showed a 14-fold stimulation above control with 5% serum that was decreased to 322%, 393%, and 313% in the presence of BMP-2 (10 ng/ml), BMP4 (10 ng/ml), and transforming growth factor (TGF)-,1 (2 ng/ml), respectively [6].
  • Here we report that BMP-4, -6, and -7 potently suppress both basal (P < 0.0001; respective IC(50) values, 0.78, 0.30, and 1.50 ng/ml) and LH-induced (P < 0.0001; respective IC(50) values, 5.00, 0.55, and 4.55 ng/ml) androgen production by bovine theca cells while having only a moderate effect on progesterone production and cell number [7].

Other interactions of BMP4

  • Gremlin and chordin were found to be effective antagonists of BMP-4 and -7, respectively, and the observation that both antagonists enhanced (P < 0.01) androgen production in the absence of exogenous BMP suggests an autocrine/paracrine role for theca-derived BMP-4 and -7 in modulating androgen production [7].
  • We evaluated the effects of GDF-9 (150-600 ng/ml) and BMP-4 (30 ng/ml) during a 2-day exposure on hormone-induced steroidogenesis and cell proliferation [8].
  • Moreover, studies on granulosa cells showed that preincubation of ligand with excess FS abolished activin-A-induced phosphorylation of Smad-2 and BMP-4-induced phosphorylation of Smad-1 [9].

Analytical, diagnostic and therapeutic context of BMP4


  1. Comparative genomics on BMP4 orthologs. Katoh, Y., Katoh, M. Int. J. Oncol. (2005) [Pubmed]
  2. Initiation and promotion of bone differentiation by bone morphogenetic proteins. Reddi, A.H., Cunningham, N.S. J. Bone Miner. Res. (1993) [Pubmed]
  3. Recombinant bone morphogenetic protein-4, transforming growth factor-beta 1, and activin A enhance the cartilage phenotype of articular chondrocytes in vitro. Luyten, F.P., Chen, P., Paralkar, V., Reddi, A.H. Exp. Cell Res. (1994) [Pubmed]
  4. Regulatory role of transforming growth factor-beta, bone morphogenetic protein-2, and protein-4 on gene expression of extracellular matrix proteins and differentiation of dental pulp cells. Nakashima, M., Nagasawa, H., Yamada, Y., Reddi, A.H. Dev. Biol. (1994) [Pubmed]
  5. Expression of bone morphogenetic protein2 (BMP2), BMP4 and BMP receptors in the bovine ovary but absence of effects of BMP2 and BMP4 during IVM on bovine oocyte nuclear maturation and subsequent embryo development. Fatehi, A.N., van den Hurk, R., Colenbrander, B., Daemen, A.J., van Tol, H.T., Monteiro, R.M., Roelen, B.A., Bevers, M.M. Theriogenology (2005) [Pubmed]
  6. Bone morphogenetic proteins-2 and -4: negative growth regulators in adult retinal pigmented epithelium. Mathura, J.R., Jafari, N., Chang, J.T., Hackett, S.F., Wahlin, K.J., Della, N.G., Okamoto, N., Zack, D.J., Campochiaro, P.A. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  7. Bone morphogenetic proteins (BMP) -4, -6, and -7 potently suppress basal and luteinizing hormone-induced androgen production by bovine theca interna cells in primary culture: could ovarian hyperandrogenic dysfunction be caused by a defect in thecal BMP signaling? Glister, C., Richards, S.L., Knight, P.G. Endocrinology (2005) [Pubmed]
  8. Growth differentiation factor-9 has divergent effects on proliferation and steroidogenesis of bovine granulosa cells. Spicer, L.J., Aad, P.Y., Allen, D., Mazerbourg, S., Hsueh, A.J. J. Endocrinol. (2006) [Pubmed]
  9. Bone morphogenetic protein (BMP) ligands and receptors in bovine ovarian follicle cells: actions of BMP-4, -6 and -7 on granulosa cells and differential modulation of Smad-1 phosphorylation by follistatin. Glister, C., Kemp, C.F., Knight, P.G. Reproduction (2004) [Pubmed]
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