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Gene Review

BMP2  -  bone morphogenetic protein 2

Homo sapiens

Synonyms: BDA2, BMP-2, BMP-2A, BMP2A, Bone morphogenetic protein 2, ...
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Disease relevance of BMP2


Psychiatry related information on BMP2


High impact information on BMP2

  • In fact, in bones lacking BMP2, the earliest steps of fracture healing seem to be blocked [6].
  • Mice lacking the ability to produce BMP2 in their limb bones have spontaneous fractures that do not resolve with time [6].
  • The genesis of vertebrate peripheral ganglia poses the problem of how multipotent neural crest stem cells (NCSCs) can sequentially generate neurons and then glia in a local environment containing strong instructive neurogenic factors, such as BMP2 [7].
  • Mesenchyme cells from Mf1lacZ embryos differentiate poorly into cartilage in micromass culture and do not respond to added BMP2 and TGFbeta1 [8].
  • BMP2 treatment results in accumulation of MADR1 in the nucleus [9].

Chemical compound and disease context of BMP2


Biological context of BMP2


Anatomical context of BMP2

  • The potency of different human BMPs in stimulating hepcidin transcription by murine primary hepatocytes is BMP9 > BMP4 > BMP2 [19].
  • Incubation of mesangial cells with increasing concentrations of BMP2 inhibited PDGF-induced DNA synthesis in a dose-dependent manner with maximum inhibition at 250 ng/ml [16].
  • Saos2 cells overexpressing mIkappaB (Saos2-mIkappaB) exhibit higher expression of osteoblast phenotypic genes such as alkaline phosphatase, Runx2 and osteocalcin and are more responsive to BMP2 in comparison to wild-type cells (Saos2-wt) or empty vector infected controls (Saos2-EV) [20].
  • Mouse myoblast cells (C2C12) transduced with this vector could produce and secrete biologically active BMP2 protein and induce osteogenic activity, which was confirmed by ELISA and alkaline phosphatase activity assay [21].
  • Colonization of human gastric mucosa with H. pylori was associated with an increase in BMP2 expression due to influx of inflammatory cells that produce BMP2 [22].

Associations of BMP2 with chemical compounds

  • In reproductive cell lines, Dragon expression enhanced signaling of exogenous BMP2 or BMP4 [23].
  • The presence or absence of osteogenic media (beta-glycerol phosphate and ascorbic acid) and/or with BMP2 did not stimulate osteoblastic gene expression in the Runx2-null cells [24].
  • During the course of perinatal development of sympathetic neurons, BRINP1 is induced from earlier embryonic stage and further increased toward adult stage, while BRINP3 expressed from earlier stage is replaced by BRINP2 expression which increases postnatally in accordance with the action of BMP2 and RA [25].
  • In BMP2 gene, AGA right curved arrow AGT transversion in exon 3, converting arginine to serine was detected [26].
  • The addition of the highest dose of BMP2 enhanced oestradiol production (P < 0.05) without affecting the proliferation of the cells [27].

Physical interactions of BMP2

  • BMP-2 effectively displaced [125]OP-1 binding to HBCs while TGF-beta 1 did not [28].
  • As the first step to test this hypothesis, we demonstrate that MGP is a binding protein for 125I-BMP-2 [29].
  • Many reviews have addressed events downstream of BMP-receptor binding but few deal with molecular cascades involved in BMP-2-induced osteogenesis [30].
  • BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II [31].
  • Furthermore, Scatchard analyses revealed that the numbers of FGF-2 binding sites were increased by approximately 40% after BMP-2 treatment [32].

Co-localisations of BMP2


Regulatory relationships of BMP2

  • These data indicate that BMP2 exposure can regulate PTEN protein levels by decreasing PTEN's association with the degradative pathway [1].
  • BMP-2 stimulated PlGF expression in MG63 cells with an EC50 of about 50 ng/ml and mRNA levels peaked between 24 and 32 h after stimulation [34].
  • BMP-6 induced a less robust cellular response than BMP-2, particularly in alginate culture [35].
  • Undecalcified sections cut for histological analysis 60 d after healing of hOP-1-treated specimens showed substantial cementogenesis with scattered remnants of the collagenous carrier. hBMP-2 applied alone induced greater amounts of mineralized bone and osteoid when compared to hOP-1 alone or to combined morphogen applications [36].
  • Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing [37].

Other interactions of BMP2

  • We found that exposure to BMP2 increased PTEN protein levels in a time- and dose-dependent manner [1].
  • BMP-2 and BMP-4 induced expression of ALK1 in a dose-dependent fashion as determined by real-time PCR and immunoblotting [38].
  • The present study shows that in addition to TGF-beta1 and -beta3, endoglin interacts with activin-A, bone morphogenetic protein (BMP)-7, and BMP-2 but requires coexpression of the respective ligand binding kinase receptor for this association [39].
  • MGP has also been identified as an inhibitor of bone morphogenetic protein-2 (BMP-2) [38].
  • RUNX2, the earliest transcription factor proven essential for commitment to osteoblastogenesis, is also expressed in response to BMP2 [15].

Analytical, diagnostic and therapeutic context of BMP2

  • This study is, to our knowledge, the first to establish the feasibility of AAV-based BMP2 gene therapy for endochondral ossification in immunocompetent animals [21].
  • MGP/BMP2 colocalization was analyzed by confocal microscopy. gamma-Carboxylation activity was measured by incorporation of 14CO2 into FLEEL synthetic peptide [33].
  • Polymerase chain reaction (PCR) and Western blotting showed that the BMP2/7 fusion gene construct led to the production of BMP2/7 heterodimers in A549 'producer' cells [40].
  • HCAECs were treated with oxidized-low density lipoprotein (ox-LDL, 80 microg/mL) or tumor necrosis factor-alpha (TNFalpha, 10 ng/mL), and the expression of Cbfa1, BMP2, and MGP was quantified by real-time PCR [41].
  • In this study, we investigated the expression of the BMP receptors (BMPRs) in sheep ovaries by immunohistochemistry and the effect of BMP2, a natural ligand for these receptors, on granulosa cells cultured in vitro [27].


  1. BMP2 exposure results in decreased PTEN protein degradation and increased PTEN levels. Waite, K.A., Eng, C. Hum. Mol. Genet. (2003) [Pubmed]
  2. Combined bone morphogenetic protein-2 and -7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model. Zhu, W., Rawlins, B.A., Boachie-Adjei, O., Myers, E.R., Arimizu, J., Choi, E., Lieberman, J.R., Crystal, R.G., Hidaka, C. J. Bone Miner. Res. (2004) [Pubmed]
  3. Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression. Horvath, L.G., Henshall, S.M., Kench, J.G., Turner, J.J., Golovsky, D., Brenner, P.C., O'Neill, G.F., Kooner, R., Stricker, P.D., Grygiel, J.J., Sutherland, R.L. Prostate (2004) [Pubmed]
  4. Sudden infant death syndrome: case-control frequency differences at genes pertinent to early autonomic nervous system embryologic development. Weese-Mayer, D.E., Berry-Kravis, E.M., Zhou, L., Maher, B.S., Curran, M.E., Silvestri, J.M., Marazita, M.L. Pediatr. Res. (2004) [Pubmed]
  5. Bone morphogenetic protein 2 (BMP-2) induces sequential changes of Id gene expression in the breast cancer cell line MCF-7. Clement, J.H., Marr, N., Meissner, A., Schwalbe, M., Sebald, W., Kliche, K.O., Höffken, K., Wölfl, S. J. Cancer Res. Clin. Oncol. (2000) [Pubmed]
  6. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Tsuji, K., Bandyopadhyay, A., Harfe, B.D., Cox, K., Kakar, S., Gerstenfeld, L., Einhorn, T., Tabin, C.J., Rosen, V. Nat. Genet. (2006) [Pubmed]
  7. Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Morrison, S.J., Perez, S.E., Qiao, Z., Verdi, J.M., Hicks, C., Weinmaster, G., Anderson, D.J. Cell (2000) [Pubmed]
  8. The forkhead/winged helix gene Mf1 is disrupted in the pleiotropic mouse mutation congenital hydrocephalus. Kume, T., Deng, K.Y., Winfrey, V., Gould, D.B., Walter, M.A., Hogan, B.L. Cell (1998) [Pubmed]
  9. MADR1, a MAD-related protein that functions in BMP2 signaling pathways. Hoodless, P.A., Haerry, T., Abdollah, S., Stapleton, M., O'Connor, M.B., Attisano, L., Wrana, J.L. Cell (1996) [Pubmed]
  10. Compactin and simvastatin, but not pravastatin, induce bone morphogenetic protein-2 in human osteosarcoma cells. Sugiyama, M., Kodama, T., Konishi, K., Abe, K., Asami, S., Oikawa, S. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  11. Alteration of gene expression in response to bone morphogenetic protein-2 in androgen-dependent human prostate cancer LNCaP cells. Kumagai, T., Tomari, K., Shimizu, T., Takeda, K. Int. J. Mol. Med. (2006) [Pubmed]
  12. Bone morphogenetic protein-2 induces hypophosphorylation of Rb protein and repression of E2F in androgen-treated LNCaP human prostate cancer cells. Tomari, K., Kumagai, T., Shimizu, T., Takeda, K. Int. J. Mol. Med. (2005) [Pubmed]
  13. Specific induction of apoptosis in P19 embryonal carcinoma cells by retinoic acid and BMP2 or BMP4. Glozak, M.A., Rogers, M.B. Dev. Biol. (1996) [Pubmed]
  14. Low expression of human tubulin tyrosine ligase and suppressed tubulin tyrosination/detyrosination cycle are associated with impaired neuronal differentiation in neuroblastomas with poor prognosis. Kato, C., Miyazaki, K., Nakagawa, A., Ohira, M., Nakamura, Y., Ozaki, T., Imai, T., Nakagawara, A. Int. J. Cancer (2004) [Pubmed]
  15. BMP2 Commitment to the Osteogenic Lineage Involves Activation of Runx2 by DLX3 and a Homeodomain Transcriptional Network. Hassan, M.Q., Tare, R.S., Lee, S.H., Mandeville, M., Morasso, M.I., Javed, A., van Wijnen, A.J., Stein, J.L., Stein, G.S., Lian, J.B. J. Biol. Chem. (2006) [Pubmed]
  16. Bone morphogenetic protein 2 inhibits platelet-derived growth factor-induced c-fos gene transcription and DNA synthesis in mesangial cells. Involvement of mitogen-activated protein kinase. Ghosh Choudhury, G., Kim, Y.S., Simon, M., Wozney, J., Harris, S., Ghosh-Choudhury, N., Abboud, H.E., Ghosh Choundhury, G., Ghosh-Choundhury, N. J. Biol. Chem. (1999) [Pubmed]
  17. A polymorphism in a conserved posttranscriptional regulatory motif alters bone morphogenetic protein 2 (BMP2) RNA:protein interactions. Fritz, D.T., Jiang, S., Xu, J., Rogers, M.B. Mol. Endocrinol. (2006) [Pubmed]
  18. Regulation of human erythropoiesis by activin A, BMP2, and BMP4, members of the TGFbeta family. Maguer-Satta, V., Bartholin, L., Jeanpierre, S., Ffrench, M., Martel, S., Magaud, J.P., Rimokh, R. Exp. Cell Res. (2003) [Pubmed]
  19. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Truksa, J., Peng, H., Lee, P., Beutler, E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  20. Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NFkappaB. Eliseev, R.A., Schwarz, E.M., Zuscik, M.J., O'Keefe, R.J., Drissi, H., Rosier, R.N. Exp. Cell Res. (2006) [Pubmed]
  21. Gene therapy for new bone formation using adeno-associated viral bone morphogenetic protein-2 vectors. Chen, Y., Luk, K.D., Cheung, K.M., Xu, R., Lin, M.C., Lu, W.W., Leong, J.C., Kung, H.F. Gene Ther. (2003) [Pubmed]
  22. Altered bone morphogenetic protein signalling in the Helicobacter pylori-infected stomach. Bleuming, S.A., Kodach, L.L., Garcia Leon, M.J., Richel, D.J., Peppelenbosch, M.P., Reitsma, P.H., Hardwick, J.C., van den Brink, G.R. J. Pathol. (2006) [Pubmed]
  23. Localization and action of Dragon (repulsive guidance molecule b), a novel bone morphogenetic protein coreceptor, throughout the reproductive axis. Xia, Y., Sidis, Y., Mukherjee, A., Samad, T.A., Brenner, G., Woolf, C.J., Lin, H.Y., Schneyer, A. Endocrinology (2005) [Pubmed]
  24. Reconstitution of Runx2/Cbfa1-null cells identifies a requirement for BMP2 signaling through a Runx2 functional domain during osteoblast differentiation. Bae, J.S., Gutierrez, S., Narla, R., Pratap, J., Devados, R., van Wijnen, A.J., Stein, J.L., Stein, G.S., Lian, J.B., Javed, A. J. Cell. Biochem. (2007) [Pubmed]
  25. Identification and characterization of novel developmentally regulated neural-specific proteins, BRINP family. Kawano, H., Nakatani, T., Mori, T., Ueno, S., Fukaya, M., Abe, A., Kobayashi, M., Toda, F., Watanabe, M., Matsuoka, I. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  26. Lack of aberrations of the BMP4, BMP2, and PTX1 genes in a patient with pituitary hypoplasia, os odontoideum, renal dysplasia, and right leg anomalies. Goto, M., Takita, J., Hashimoto, N., Tateshita, F., Toyoji, H., Kato, H., Egi, S., Hayashi, Y. Int. J. Mol. Med. (2002) [Pubmed]
  27. Effect of bone morphogenetic protein 2 (BMP2) on oestradiol and inhibin A production by sheep granulosa cells, and localization of BMP receptors in the ovary by immunohistochemistry. Souza, C.J., Campbell, B.K., McNeilly, A.S., Baird, D.T. Reproduction (2002) [Pubmed]
  28. Evidence that human bone cells in culture contain binding sites for osteogenic protein-1. Malpe, R., Baylink, D.J., Sampath, T.K., Mohan, S. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  29. Modulation of the binding of matrix Gla protein (MGP) to bone morphogenetic protein-2 (BMP-2). Wallin, R., Cain, D., Hutson, S.M., Sane, D.C., Loeser, R. Thromb. Haemost. (2000) [Pubmed]
  30. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Ryoo, H.M., Lee, M.H., Kim, Y.J. Gene (2006) [Pubmed]
  31. BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II. Kirsch, T., Nickel, J., Sebald, W. EMBO J. (2000) [Pubmed]
  32. BMP-2 augments FGF-induced differentiation of PC12 cells through upregulation of FGF receptor-1 expression. Hayashi, H., Ishisaki, A., Suzuki, M., Imamura, T. J. Cell. Sci. (2001) [Pubmed]
  33. Matrix GLA protein function in human trabecular meshwork cells: inhibition of BMP2-induced calcification process. Xue, W., Wallin, R., Olmsted-Davis, E.A., Borrás, T. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  34. Bone morphogenetic protein 2 induces placental growth factor in mesenchymal stem cells. Marrony, S., Bassilana, F., Seuwen, K., Keller, H. Bone (2003) [Pubmed]
  35. Gene-mediated osteogenic differentiation of stem cells by bone morphogenetic proteins-2 or -6. Zachos, T.A., Shields, K.M., Bertone, A.L. J. Orthop. Res. (2006) [Pubmed]
  36. Periodontal tissue regeneration by combined applications of recombinant human osteogenic protein-1 and bone morphogenetic protein-2. A pilot study in Chacma baboons (Papio ursinus). Ripamonti, U., Crooks, J., Petit, J.C., Rueger, D.C. Eur. J. Oral Sci. (2001) [Pubmed]
  37. Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing. Bouletreau, P.J., Warren, S.M., Spector, J.A., Peled, Z.M., Gerrets, R.P., Greenwald, J.A., Longaker, M.T. Plast. Reconstr. Surg. (2002) [Pubmed]
  38. Regulation of Bone Morphogenetic Protein-4 by Matrix GLA Protein in Vascular Endothelial Cells Involves Activin-like Kinase Receptor 1. Yao, Y., Zebboudj, A.F., Shao, E., Perez, M., Bostr??m, K. J. Biol. Chem. (2006) [Pubmed]
  39. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily. Barbara, N.P., Wrana, J.L., Letarte, M. J. Biol. Chem. (1999) [Pubmed]
  40. Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro. Zhu, W., Kim, J., Cheng, C., Rawlins, B.A., Boachie-Adjei, O., Crystal, R.G., Hidaka, C. Bone (2006) [Pubmed]
  41. Regulatory role of endothelium in the expression of genes affecting arterial calcification. Cola, C., Almeida, M., Li, D., Romeo, F., Mehta, J.L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
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