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Gene Review

Bmp2  -  bone morphogenetic protein 2

Mus musculus

Synonyms: AI467020, BMP-2, BMP-2A, Bmp-2, Bmp2a, ...
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Disease relevance of Bmp2

  • Both the fetal and adult compound-deficient mice showed a reduction in the trabecular bone volume with suppressed bone formation, but normal bone resorption, whereas the single deficient mice (Bmp2+/- or Bmp6-/-) did not [1].
  • These findings suggest that BMP-2, in concert with TNF, plays an essential role in regulating the regeneration of peripheral nerves following injury with bone fracture through an indirect mechanism by which it stimulates NGF production in fibroblasts [2].
  • Using retroviruses or beads to increase Fibroblast Growth Factors (FGFs) for gain-of-function and beads soaked with the FGF inhibitor SU5402 for loss-of-function experiments, we show that FGFs in the crista promote canal development by upregulating Bmp2 [3].
  • Transcriptional regulation of the Bmp2 gene. Retinoic acid induction in F9 embryonal carcinoma cells and Saccharomyces cerevisiae [4].
  • Hypoxia promoted bone morphogenetic protein 2-induced glycosaminoglycan production and suppressed alkaline phosphatase activity and mineralization of C3H10T1/2 [5].

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].
  • Lack of Fgf8 in the apical ectodermal ridge (AER) alters expression of other Fgf genes, Shh and Bmp2 [7].
  • We demonstrate that bone morphogenic protein 2 (BMP2) induces the basic-helix-loop-helix protein MASH1 and neurogenesis in neural crest stem cells [8].
  • Some smooth muscle differentiation is also observed in BMP2 [8].

Chemical compound and disease context of Bmp2


Biological context of Bmp2


Anatomical context of Bmp2

  • To address the function of bone morphogenetic protein-2 (BMP2) in mammalian development, mice with a targeted deletion of the Bmp2 mature region were generated using embryonic stem cell technology [15].
  • These defects are consistent with the expression of Bmp2 in the extraembryonic mesoderm cells and promyocardium [15].
  • In further analyses, we have identified Bmp2 as the factor required for production of migratory cranial neural crest [16].
  • In the Hesr1-misexpressing heart, the boundaries of the AV canal are poorly defined, and the expression levels of specific markers of the AV myocardium, Bmp2 and Tbx2, are either very weak or undetectable [17].
  • In addition, we provide evidence that Hedgehog signaling, acting at the Shh boundary within the oral ectoderm, may exert a role in differentiation of ventral cell types (gonadotropes and thyrotropes) by inducing Bmp2 expression in Rathke's pouch, which subsequently regulates expression of ventral transcription factors, particularly Gata2 [18].

Associations of Bmp2 with chemical compounds


Physical interactions of Bmp2

  • Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T 1/2 mesenchymal cells [24].
  • Electrophoresis mobility shift assays indicated that BMP2 treatment on C3H10T1/2 cells increases the binding of cell nuclear extracts to the -148/-42 fragment, and the BMP2-enhanced binding bands are Sp1 transcription factors [25].
  • These data indicate that the extracellular domain of type I receptor for BMP-2 and BMP-4 is sufficient for high-affinity binding to its ligands and should prove useful in understanding the role of BMP-2/4 in vivo, because a suitable high-affinity anti-BMP antibody has yet to be developed [26].

Regulatory relationships of Bmp2


Other interactions of Bmp2

  • FGF-4 and BMP-2 have opposite effects on limb growth [30].
  • Subsequently, a BMP2 signal emanates from a ventral pituitary organizing center that forms at the boundary of a region of oral ectoderm in which Shh expression is selectively excluded [31].
  • The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling [14].
  • As a result, genes such as Bmp2 or Hoxd genes are expressed symmetrically along the AP axis of the forelimb buds, and/or later, of the autopod [32].
  • There is a close relationship, both temporal and spatial, between the activation of the Bmp-2 and Hoxd-13 genes in response to retinoic acid and polarizing region grafts, suggesting that expression of the two genes might be linked [19].

Analytical, diagnostic and therapeutic context of Bmp2


  1. Involvement of endogenous bone morphogenetic protein (BMP) 2 and BMP6 in bone formation. Kugimiya, F., Kawaguchi, H., Kamekura, S., Chikuda, H., Ohba, S., Yano, F., Ogata, N., Katagiri, T., Harada, Y., Azuma, Y., Nakamura, K., Chung, U.I. J. Biol. Chem. (2005) [Pubmed]
  2. Bone morphogenetic protein-2 is markedly synergistic with tumor necrosis factor in stimulating the production of nerve growth factor in fibroblasts. Hattorl, A., Tsujimoto, M., Hayashi, K., Kohno, M. Biochem. Mol. Biol. Int. (1996) [Pubmed]
  3. The development of semicircular canals in the inner ear: role of FGFs in sensory cristae. Chang, W., Brigande, J.V., Fekete, D.M., Wu, D.K. Development (2004) [Pubmed]
  4. Transcriptional regulation of the Bmp2 gene. Retinoic acid induction in F9 embryonal carcinoma cells and Saccharomyces cerevisiae. Heller, L.C., Li, Y., Abrams, K.L., Rogers, M.B. J. Biol. Chem. (1999) [Pubmed]
  5. Oxygen Tension Regulates Chondrocyte Differentiation and Function during Endochondral Ossification. Hirao, M., Tamai, N., Tsumaki, N., Yoshikawa, H., Myoui, A. J. Biol. Chem. (2006) [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. Fgf8 is required for outgrowth and patterning of the limbs. Moon, A.M., Capecchi, M.R. Nat. Genet. (2000) [Pubmed]
  8. Alternative neural crest cell fates are instructively promoted by TGFbeta superfamily members. Shah, N.M., Groves, A.K., Anderson, D.J. Cell (1996) [Pubmed]
  9. Isolation and characterization of a mesenchymal cell line that differentiates into osteoblasts in response to BMP-2 from calvariae of GFP transgenic mice. Kadowaki, A., Tsukazaki, T., Hirata, K., Shibata, Y., Okubo, Y., Bessho, K., Komori, T., Yoshida, N., Yamaguchi, A. Bone (2004) [Pubmed]
  10. Regulation of the laminin beta 1 (LAMB1), retinoic acid receptor beta, and bone morphogenetic protein 2 genes in mutant F9 teratocarcinoma cell lines partially deficient in cyclic AMP-dependent protein kinase activity. Shen, J., Li, C., Gudas, L.J. Cell Growth Differ. (1997) [Pubmed]
  11. Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice. Jiang, R., Lan, Y., Chapman, H.D., Shawber, C., Norton, C.R., Serreze, D.V., Weinmaster, G., Gridley, T. Genes Dev. (1998) [Pubmed]
  12. Developmental patterning of the cardiac atrioventricular canal by Notch and Hairy-related transcription factors. Rutenberg, J.B., Fischer, A., Jia, H., Gessler, M., Zhong, T.P., Mercola, M. Development (2006) [Pubmed]
  13. Runx2 regulates FGF2-induced Bmp2 expression during cranial bone development. Choi, K.Y., Kim, H.J., Lee, M.H., Kwon, T.G., Nah, H.D., Furuichi, T., Komori, T., Nam, S.H., Kim, Y.J., Kim, H.J., Ryoo, H.M. Dev. Dyn. (2005) [Pubmed]
  14. The zinc finger transcription factor Gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling. Zhao, M., Qiao, M., Harris, S.E., Chen, D., Oyajobi, B.O., Mundy, G.R. Mol. Cell. Biol. (2006) [Pubmed]
  15. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Zhang, H., Bradley, A. Development (1996) [Pubmed]
  16. BMP signaling is essential for development of skeletogenic and neurogenic cranial neural crest. Kanzler, B., Foreman, R.K., Labosky, P.A., Mallo, M. Development (2000) [Pubmed]
  17. Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2. Kokubo, H., Tomita-Miyagawa, S., Hamada, Y., Saga, Y. Development (2007) [Pubmed]
  18. Hedgehog signaling is required for pituitary gland development. Treier, M., O'Connell, S., Gleiberman, A., Price, J., Szeto, D.P., Burgess, R., Chuang, P.T., McMahon, A.P., Rosenfeld, M.G. Development (2001) [Pubmed]
  19. Bone morphogenetic proteins and a signalling pathway that controls patterning in the developing chick limb. Francis, P.H., Richardson, M.K., Brickell, P.M., Tickle, C. Development (1994) [Pubmed]
  20. Inhibins differentially antagonize activin and bone morphogenetic protein action in a mouse adrenocortical cell line. Farnworth, P.G., Stanton, P.G., Wang, Y., Escalona, R., Findlay, J.K., Ooi, G.T. Endocrinology (2006) [Pubmed]
  21. 1-(5-oxohexyl)-3,7-Dimethylxanthine, a phosphodiesterase inhibitor, activates MAPK cascades and promotes osteoblast differentiation by a mechanism independent of PKA activation (pentoxifylline promotes osteoblast differentiation). Rawadi, G., Ferrer, C., Spinella-Jaegle, S., Roman-Roman, S., Bouali, Y., Baron, R. Endocrinology (2001) [Pubmed]
  22. Overexpression of twisted gastrulation inhibits bone morphogenetic protein action and prevents osteoblast cell differentiation in vitro. Gazzerro, E., Deregowski, V., Vaira, S., Canalis, E. Endocrinology (2005) [Pubmed]
  23. Bone morphogenetic protein-2 enhances osteoclast formation mediated by interleukin-1alpha through upregulation of osteoclast differentiation factor and cyclooxygenase-2. Koide, M., Murase, Y., Yamato, K., Noguchi, T., Okahashi, N., Nishihara, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  24. Parathyroid hormone-related peptide interacts with bone morphogenetic protein 2 to increase osteoblastogenesis and decrease adipogenesis in pluripotent C3H10T 1/2 mesenchymal cells. Chan, G.K., Miao, D., Deckelbaum, R., Bolivar, I., Karaplis, A., Goltzman, D. Endocrinology (2003) [Pubmed]
  25. The role of Sp1 in BMP2-up-regulated Erk2 gene expression. Xing, X., Manske, P.R., Li, Y.Y., Lou, J. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  26. Interaction between soluble type I receptor for bone morphogenetic protein and bone morphogenetic protein-4. Natsume, T., Tomita, S., Iemura, S., Kinto, N., Yamaguchi, A., Ueno, N. J. Biol. Chem. (1997) [Pubmed]
  27. Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation. Lee, M.H., Javed, A., Kim, H.J., Shin, H.I., Gutierrez, S., Choi, J.Y., Rosen, V., Stein, J.L., van Wijnen, A.J., Stein, G.S., Lian, J.B., Ryoo, H.M. J. Cell. Biochem. (1999) [Pubmed]
  28. Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis. Hata, K., Nishimura, R., Ikeda, F., Yamashita, K., Matsubara, T., Nokubi, T., Yoneda, T. Mol. Biol. Cell (2003) [Pubmed]
  29. Bone morphogenetic protein-2 converts the differentiation pathway of C2C12 myoblasts into the osteoblast lineage. Katagiri, T., Yamaguchi, A., Komaki, M., Abe, E., Takahashi, N., Ikeda, T., Rosen, V., Wozney, J.M., Fujisawa-Sehara, A., Suda, T. J. Cell Biol. (1994) [Pubmed]
  30. FGF-4 and BMP-2 have opposite effects on limb growth. Niswander, L., Martin, G.R. Nature (1993) [Pubmed]
  31. Multistep signaling requirements for pituitary organogenesis in vivo. Treier, M., Gleiberman, A.S., O'Connell, S.M., Szeto, D.P., McMahon, J.A., McMahon, A.P., Rosenfeld, M.G. Genes Dev. (1998) [Pubmed]
  32. Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse. Niederreither, K., Vermot, J., Schuhbaur, B., Chambon, P., Dollé, P. Development (2002) [Pubmed]
  33. Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Ying, Y., Zhao, G.Q. Dev. Biol. (2001) [Pubmed]
  34. Generation of a Bmp2 conditional null allele. Ma, L., Martin, J.F. Genesis (2005) [Pubmed]
  35. Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP-2. Yuasa, T., Kataoka, H., Kinto, N., Iwamoto, M., Enomoto-Iwamoto, M., Iemura, S., Ueno, N., Shibata, Y., Kurosawa, H., Yamaguchi, A. J. Cell. Physiol. (2002) [Pubmed]
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