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Gene Review

Bmp2  -  bone morphogenetic protein 2

Rattus norvegicus

Synonyms: BMP-2, BMP-2A, Bmp-2, Bone morphogenetic protein 2, Bone morphogenetic protein 2A
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Disease relevance of Bmp2

  • To investigate a possible biological function of the pro-form of bone morphogenetic protein (BMP)-2, a member of the TGF-beta family, mature BMP-2, proBMP-2, and the isolated pro-peptide were recombinantly produced in Escherichia coli cells, and a biophysical comparison was performed [1].
  • After 0.5 and 3 days of exposure to hypoxia, upregulation of BMP-2 was observed in the intrapulmonary arteries [2].
  • Inflammatory changes and fibrosis lead to delayed healing, triggered by bone morphogentic protein 2/4 (BMP2/4) and transforming growth factor (TGF)-beta(1) [3].
  • In particular, growth/differentiation factor-5, bone morphogenetic protein-2, -4, -7 and -12 significantly increased the survival promoting effects of neurotrophin-3 and nerve growth factor on cultured dorsal root ganglion neurons [4].
  • After twenty-four hours, each defect received a single, intralesional, percutaneous injection of adenovirus carrying bone morphogenetic protein-2 (Ad.BMP-2) or luciferase cDNA (Ad.luc) or it remained untreated [5].

Psychiatry related information on Bmp2


High impact information on Bmp2

  • The effects of BMP-2 on noggin transcripts were dependent on protein, but independent of DNA synthesis [7].
  • By contrast, if the cells are exposed to saturating concentrations of both BMP2 and transforming growth factor beta1 (which promotes smooth muscle differentiation), the two factors appear codominant [8].
  • Bone morphogenetic protein 2 (BMP-2), which induces osteoblast function, does not alter TGF-beta binding or biochemical activity in fibroblasts and has only small effects in less differentiated bone cells [9].
  • Pretreatment with BMP-2 diminishes TGF-beta-induced DNA synthesis in osteoblast-enriched cultures but synergistically enhances its stimulatory effects on either collagen synthesis or alkaline phosphatase activity, depending on the present state of bone cell differentiation [9].
  • Independent changes in type I and type II receptors for transforming growth factor beta induced by bone morphogenetic protein 2 parallel expression of the osteoblast phenotype [9].

Biological context of Bmp2


Anatomical context of Bmp2


Associations of Bmp2 with chemical compounds


Enzymatic interactions of Bmp2

  • Moreover, BMP-2 induced phosphorylated Trk immunoreactivity in cultured striatal neurones, suggesting that neurotrophins are involved in BMP-2 neurotrophic effects [20].

Regulatory relationships of Bmp2

  • In conclusion, BMP-2 inhibits IGFBP-5 expression in Ob cells through pathways that are independent of its mitogenic activity and through mechanisms that may involve decreased transcription or altered RNA processing [21].
  • Moreover, the effects of both TGFbeta(1) and BMP-2 on alpha1(I) collagen gene expression were markedly decreased in transfected ROS 17/2.8 cells expressing a dominant-negative MEK-1 [22].
  • Bone morphogenetic protein-2 inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of the Smad1 pathway [23].
  • We propose that the induction of BMP-2 and -4 and their receptor by GH compliments the role of GH-induced insulin-like growth factor 1 (IGF-1) in promoting bone and tooth root formation [24].
  • In conclusion, this study demonstrates that BMP-2 and TGFbeta1 suppress collagenase-3 promoter activity in osteoblasts and establishes a link between BMP-2 action and collagenase-3 expression via Runx2, a major regulator of osteoblast formation and function [25].

Other interactions of Bmp2

  • Continuous or 24-h exposure to BMP-2 or -4 increased the number of postmitotic ALP-positive cells in log phase cultures, whereas BMP-6 increased the number of postmitotic ALP-negative cells [10].
  • BMP-2 showed reduced potency compared to either BMP-4 or -6 [10].
  • Adjacent sections examined for BMP 2/4 expression established a close temporal and spatial correlation with ERK 1/2 [14].
  • The expression of BMP2/4 subsequently increased the phosphorylation of downstream effector Smad1 and the expression of notch signal pathway-induced protein Hes1 in cultured SVZ neurospheres [26].
  • The temporospatial expression of BMPs and receptors at the injured growth plate suggests potential involvement of BMP-3 and -4 in regulating the inflammatory response or as its mediators in modulating downstream events, and BMP-2, -3, -4, and -7 in the fibrogenic and osteogenic responses, and BMP-7 in bone remodeling at the injured growth plate [27].

Analytical, diagnostic and therapeutic context of Bmp2


  1. Biophysical comparison of BMP-2, ProBMP-2, and the free pro-peptide reveals stabilization of the pro-peptide by the mature growth factor. Hillger, F., Herr, G., Rudolph, R., Schwarz, E. J. Biol. Chem. (2005) [Pubmed]
  2. Downregulation of type II bone morphogenetic protein receptor in hypoxic pulmonary hypertension. Takahashi, H., Goto, N., Kojima, Y., Tsuda, Y., Morio, Y., Muramatsu, M., Fukuchi, Y. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  3. Expression of bone morphogenic protein 2/4, transforming growth factor-beta1, and bone matrix protein expression in healing area between vascular tibia grafts and irradiated bone-experimental model of osteonecrosis. Schultze-Mosgau, S., Lehner, B., Rödel, F., Wehrhan, F., Amann, K., Kopp, J., Thorwarth, M., Nkenke, E., Grabenbauer, G. Int. J. Radiat. Oncol. Biol. Phys. (2005) [Pubmed]
  4. Characterization of bone morphogenetic protein family members as neurotrophic factors for cultured sensory neurons. Farkas, L.M., Jászai, J., Unsicker, K., Krieglstein, K. Neuroscience (1999) [Pubmed]
  5. Direct percutaneous gene delivery to enhance healing of segmental bone defects. Betz, O.B., Betz, V.M., Nazarian, A., Pilapil, C.G., Vrahas, M.S., Bouxsein, M.L., Gerstenfeld, L.C., Einhorn, T.A., Evans, C.H. The Journal of bone and joint surgery. American volume. (2006) [Pubmed]
  6. Bone morphogenetic protein-2, but not bone morphogenetic protein-7, promotes dendritic growth and calbindin phenotype in cultured rat striatal neurons. Gratacòs, E., Checa, N., Alberch, J. Neuroscience (2001) [Pubmed]
  7. Bone morphogenetic proteins induce the expression of noggin, which limits their activity in cultured rat osteoblasts. Gazzerro, E., Gangji, V., Canalis, E. J. Clin. Invest. (1998) [Pubmed]
  8. Integration of multiple instructive cues by neural crest stem cells reveals cell-intrinsic biases in relative growth factor responsiveness. Shah, N.M., Anderson, D.J. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  9. Independent changes in type I and type II receptors for transforming growth factor beta induced by bone morphogenetic protein 2 parallel expression of the osteoblast phenotype. Centrella, M., Casinghino, S., Kim, J., Pham, T., Rosen, V., Wozney, J., McCarthy, T.L. Mol. Cell. Biol. (1995) [Pubmed]
  10. The effects of bone morphogenetic protein-2, -4, and -6 on differentiation of rat osteoblast cells in vitro. Hughes, F.J., Collyer, J., Stanfield, M., Goodman, S.A. Endocrinology (1995) [Pubmed]
  11. Bone morphogenetic protein-2 induces proinflammatory endothelial phenotype. Csiszar, A., Ahmad, M., Smith, K.E., Labinskyy, N., Gao, Q., Kaley, G., Edwards, J.G., Wolin, M.S., Ungvari, Z. Am. J. Pathol. (2006) [Pubmed]
  12. Krüppel-like factor 4 (KLF4/GKLF) is a target of bone morphogenetic proteins and transforming growth factor beta 1 in the regulation of vascular smooth muscle cell phenotype. King, K.E., Iyemere, V.P., Weissberg, P.L., Shanahan, C.M. J. Biol. Chem. (2003) [Pubmed]
  13. Bone marrow stromal cells upregulate expression of bone morphogenetic proteins 2 and 4, gap junction protein connexin-43 and synaptophysin after stroke in rats. Zhang, C., Li, Y., Chen, J., Gao, Q., Zacharek, A., Kapke, A., Chopp, M. Neuroscience (2006) [Pubmed]
  14. Extracellular signal-related kinase and bone morphogenetic protein expression during distraction osteogenesis of the mandible: in vivo evidence of a mechanotransduction mechanism for differentiation and osteogenesis by mesenchymal precursor cells. Rhee, S.T., El-Bassiony, L., Buchman, S.R. Plast. Reconstr. Surg. (2006) [Pubmed]
  15. A comparative histologic analysis of tissue-engineered bone using platelet-rich plasma and platelet-enriched fibrin glue. Zhu, S.J., Choi, B.H., Jung, J.H., Lee, S.H., Huh, J.Y., You, T.M., Lee, H.J., Li, J. Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics. (2006) [Pubmed]
  16. Differential effects and glucocorticoid potentiation of bone morphogenetic protein action during rat osteoblast differentiation in vitro. Boden, S.D., McCuaig, K., Hair, G., Racine, M., Titus, L., Wozney, J.M., Nanes, M.S. Endocrinology (1996) [Pubmed]
  17. Bone morphogenetic proteins: neurotrophic roles for midbrain dopaminergic neurons and implications of astroglial cells. Jordan, J., Böttner, M., Schluesener, H.J., Unsicker, K., Krieglstein, K. Eur. J. Neurosci. (1997) [Pubmed]
  18. Influence of hormones and growth factors on lens protein composition: the effect of dexamethasone and PDGF-AA. Vinader, L.M., van Genesen, S.T., de Jong, W.W., Lubsen, N.H. Mol. Vis. (2003) [Pubmed]
  19. Comparison of BMP-2 and -4 for rat mandibular bone regeneration at various doses. Arosarena, O., Collins, W. Orthodontics & craniofacial research. (2005) [Pubmed]
  20. Brain-derived neurotrophic factor (BDNF) mediates bone morphogenetic protein-2 (BMP-2) effects on cultured striatal neurones. Gratacòs, E., Checa, N., Pérez-Navarro, E., Alberch, J. J. Neurochem. (2001) [Pubmed]
  21. Bone morphogenetic protein-2 inhibits the synthesis of insulin-like growth factor-binding protein-5 in bone cell cultures. Gabbitas, B., Canalis, E. Endocrinology (1995) [Pubmed]
  22. Protein kinase signalling pathways involved in the up-regulation of the rat alpha1(I) collagen gene by transforming growth factor beta1 and bone morphogenetic protein 2 in osteoblastic cells. Palcy, S., Goltzman, D. Biochem. J. (1999) [Pubmed]
  23. Bone morphogenetic protein-2 inhibits serum deprivation-induced apoptosis of neonatal cardiac myocytes through activation of the Smad1 pathway. Izumi, M., Fujio, Y., Kunisada, K., Negoro, S., Tone, E., Funamoto, M., Osugi, T., Oshima, Y., Nakaoka, Y., Kishimoto, T., Yamauchi-Takihara, K., Hirota, H. J. Biol. Chem. (2001) [Pubmed]
  24. Growth hormone induces bone morphogenetic proteins and bone-related proteins in the developing rat periodontium. Li, H., Bartold, P.M., Young, W.G., Xiao, Y., Waters, M.J. J. Bone Miner. Res. (2001) [Pubmed]
  25. Bone morphogenetic protein-2 suppresses collagenase-3 promoter activity in osteoblasts through a runt domain factor 2 binding site. Varghese, S., Rydziel, S., Canalis, E. J. Cell. Physiol. (2005) [Pubmed]
  26. Bone marrow stromal cells induce BMP2/4 production in oxygen-glucose-deprived astrocytes, which promotes an astrocytic phenotype in adult subventricular progenitor cells. Xin, H., Li, Y., Chen, X., Chopp, M. J. Neurosci. Res. (2006) [Pubmed]
  27. Expression of bone morphogenic proteins and receptors at the injured growth plate cartilage in young rats. Ngo, T.Q., Scherer, M.A., Zhou, F.H., Foster, B.K., Xian, C.J. J. Histochem. Cytochem. (2006) [Pubmed]
  28. Faulty bone morphogenetic protein signaling in esophageal atresia with tracheoesophageal fistula. Crowley, A.R., Mehta, S.S., Hembree, M.J., Preuett, B.L., Prasadan, K.L., Sharp, S.W., Yew, H., McFall, C.R., Benjes, C.L., Tulachan, S.S., Gittes, G.K., Snyder, C.L. J. Pediatr. Surg. (2006) [Pubmed]
  29. Mechanical tension-stress induces expression of bone morphogenetic protein (BMP)-2 and BMP-4, but not BMP-6, BMP-7, and GDF-5 mRNA, during distraction osteogenesis. Sato, M., Ochi, T., Nakase, T., Hirota, S., Kitamura, Y., Nomura, S., Yasui, N. J. Bone Miner. Res. (1999) [Pubmed]
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