Bone morphogenetic protein 2

PDB rendering based on 3bmp.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1ES7, 1REU, 1REW, 2GOO, 2H62, 2H64, 2QJ9, 2QJA, 2QJB, 3BK3, 3BMP, 4MID, 4N1D, 4UHY, 4UHZ, 4UI0, 4UI1, 4UI2

Identifiers

Symbols

BMP2 ; BDA2; BMP2A

External IDs

OMIM: 112261 MGI: 88177 HomoloGene: 926 GeneCards: BMP2 Gene

Gene ontology
Molecular function	• retinol dehydrogenase activity • receptor binding • cytokine activity • transforming growth factor beta receptor binding • protein binding • growth factor activity • phosphatase activator activity • co-receptor binding • SMAD binding • protein heterodimerization activity • BMP receptor binding
Cellular component	• extracellular region • extracellular space • cell surface • BMP receptor complex
Biological process	• negative regulation of transcription from RNA polymerase II promoter • activation of MAPK activity • skeletal system development • osteoblast differentiation • branching involved in ureteric bud morphogenesis • response to hypoxia • in utero embryonic development • epithelial to mesenchymal transition • positive regulation of protein phosphorylation • positive regulation of endothelial cell proliferation • chondrocyte differentiation • BMP signaling pathway involved in heart induction • atrioventricular valve morphogenesis • endocardial cushion morphogenesis • negative regulation of Wnt signaling pathway involved in heart development • proteoglycan metabolic process • regulation of transcription, DNA-templated • protein phosphorylation • inflammatory response • Notch signaling pathway • cell-cell signaling • heart development • negative regulation of cell proliferation • embryo development • organ morphogenesis • positive regulation of gene expression • positive regulation of epithelial to mesenchymal transition • positive regulation of pathway-restricted SMAD protein phosphorylation • negative regulation of steroid biosynthetic process • positive regulation of phosphatase activity • telencephalon development • telencephalon regionalization • positive regulation of Wnt signaling pathway • extracellular matrix organization • bone mineralization • positive regulation of cell migration • positive regulation of bone mineralization • BMP signaling pathway • protein destabilization • positive regulation of protein binding • negative regulation of aldosterone biosynthetic process • positive regulation of osteoblast proliferation • cardiocyte differentiation • embryonic heart tube anterior/posterior pattern specification • bone mineralization involved in bone maturation • growth • odontogenesis of dentin-containing tooth • positive regulation of odontogenesis • regulation of odontogenesis of dentin-containing tooth • positive regulation of apoptotic process • positive regulation of MAPK cascade • negative regulation of insulin-like growth factor receptor signaling pathway • cell fate commitment • positive regulation of fat cell differentiation • positive regulation of neuron differentiation • positive regulation of osteoblast differentiation • positive regulation of ossification • negative regulation of cell cycle • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • cell development • positive regulation of astrocyte differentiation • mesenchymal cell differentiation • inner ear development • negative regulation of calcium-independent cell-cell adhesion • cardiac muscle cell differentiation • cardiac muscle tissue morphogenesis • oxidation-reduction process • pericardium development • corticotropin hormone secreting cell differentiation • thyroid-stimulating hormone-secreting cell differentiation • cardiac epithelial to mesenchymal transition • pathway-restricted SMAD protein phosphorylation • SMAD protein signal transduction • mesenchyme development • positive regulation of Wnt signaling pathway by BMP signaling pathway • positive regulation of cartilage development • positive regulation of ERK1 and ERK2 cascade • cellular response to organic cyclic compound • cellular response to BMP stimulus • mesenchymal cell proliferation involved in ureteric bud development • negative regulation of canonical Wnt signaling pathway • positive regulation of p38MAPK cascade • positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus • negative regulation of cortisol biosynthetic process • negative regulation of cardiac muscle cell differentiation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

650

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 20:
6.77 – 6.78 Mb

Chr 2:
133.55 – 133.56 Mb

PubMed search

Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.^[1]

Function

BMP-2 like other bone morphogenetic proteins,^[2] plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is involved also in cardiac cell differentiation and epithelial to mesenchymal transition.

BMP-2 and BMP-7 are osteoinductive BMPs: they have been demonstrated to potently induce osteoblast differentiation in a variety of cell types.^[3]

Interactions

Bone morphogenetic protein 2 has been shown to interact with BMPR1A.^[4]^[5]^[6]^[7]

Clinical use and complications

Bone morphogenetic protein 2 is shown to stimulate the production of bone.^[8] Recombinant human protein (rhBMP-2) is currently available for orthopaedic usage in the United States.^[9] Implantation of BMP-2 in a collagen sponge induces new bone formation and can be used for the treatment of bony defects, delayed union, and non-union.^[10]

Bone morphogenetic protein 2 has also found its way into the field of Dentistry.^[11]^[12]^[13] The use of dual tapered threaded fusion cages and recombinant human bone morphogenetic protein-2 on an absorbable collagen sponge obtained and maintained intervertebral spinal fusion, improved clinical outcomes, and reduced pain after anterior lumbar interbody arthrodesis in patients with degenerative lumbar disc disease.^[14] As an adjuvant to allograft bone or as a replacement for harvested autograft, bone morphogenetic proteins (BMPs) appear to improve fusion rates after spinal arthrodesis in both animal models and humans, while reducing the donor-site morbidity previously associated with such procedures.^[15]

A study published in 2011 noted "reports of frequent and occasionally catastrophic complications associated with use of [BMP-2] in spinal fusion surgeries", with a level of risk far in excess of estimates reported in earlier studies.^[16]^[17]

References

↑ Sampath TK, Coughlin JE, Whetstone RM, Banach D, Corbett C, Ridge RJ, Ozkaynak E, Oppermann H, Rueger DC (August 1990). "Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily". J. Biol. Chem. 265 (22): 13198–205. PMID 2376592.
↑ Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic proteins". Growth Factors 22 (4): 233–41. doi:10.1080/08977190412331279890. PMID 15621726.
↑ Marie PJ, Debiais F, Haÿ E (2002). "Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling". Histol. Histopathol. 17 (3): 877–85. PMID 12168799.
↑ Nickel J, Dreyer MK, Kirsch T, Sebald W (2001). "The crystal structure of the BMP-2:BMPR-IA complex and the generation of BMP-2 antagonists". J Bone Joint Surg Am. 83-A Suppl 1 (Pt 1): S7–14. PMID 11263668.
↑ Kirsch T, Nickel J, Sebald W (February 2000). "Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP-2". FEBS Lett. 468 (2-3): 215–9. doi:10.1016/S0014-5793(00)01214-X. PMID 10692589.
↑ Kirsch T, Nickel J, Sebald W (July 2000). "BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II". EMBO J. 19 (13): 3314–24. doi:10.1093/emboj/19.13.3314. PMC 313944. PMID 10880444.
↑ Gilboa L, Nohe A, Geissendörfer T, Sebald W, Henis YI, Knaus P (March 2000). "Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors". Mol. Biol. Cell 11 (3): 1023–35. doi:10.1091/mbc.11.3.1023. PMC 14828. PMID 10712517.
↑ Urist MR (1965). "Bone: formation by autoinduction". Science 150 (3698): 893–9. doi:10.1126/science.150.3698.893. PMID 5319761.
↑ Khan SN, Lane JM (May 2004). "The use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in orthopaedic applications". Expert Opin Biol Ther 4 (5): 741–8. doi:10.1517/14712598.4.5.741. PMID 15155165.
↑ Geiger M, Li RH, Friess W (November 2003). "Collagen sponges for bone regeneration with rhBMP-2". Adv. Drug Deliv. Rev. 55 (12): 1613–29. doi:10.1016/j.addr.2003.08.010. PMID 14623404.
↑ Allegrini S, Yoshimoto M, Salles MB, König B (February 2004). "Bone regeneration in rabbit sinus lifting associated with bovine BMP". J. Biomed. Mater. Res. Part B Appl. Biomater. 68 (2): 127–31. doi:10.1002/jbm.b.20006. PMID 14737759.
↑ Schlegel KA, Thorwarth M, Plesinac A, Wiltfang J, Rupprecht S (December 2006). "Expression of bone matrix proteins during the osseus healing of topical conditioned implants: an experimental study". Clin Oral Implants Res 17 (6): 666–72. doi:10.1111/j.1600-0501.2006.01214.x. PMID 17092225.
↑ Schliephake H, Aref A, Scharnweber D, Bierbaum S, Roessler S, Sewing A (October 2005). "Effect of immobilized bone morphogenic protein 2 coating of titanium implants on peri-implant bone formation". Clin Oral Implants Res 16 (5): 563–9. doi:10.1111/j.1600-0501.2005.01143.x. PMID 16164462.
↑ Burkus JK, Gornet MF, Schuler TC, Kleeman TJ, Zdeblick TA (May 2009). "Six-year outcomes of anterior lumbar interbody arthrodesis with use of interbody fusion cages and recombinant human bone morphogenetic protein-2". J Bone Joint Surg Am 91 (5): 1181–9. doi:10.2106/JBJS.G.01485. PMID 19411467.
↑ Subach BR, Haid RW, Rodts GE, Kaiser MG (2001). "Bone morphogenetic protein in spinal fusion: overview and clinical update". Neurosurg Focus 10 (4): E3. doi:10.3171/foc.2001.10.4.4. PMID 16732630.
↑ Richter R (2011-06-28). "Medtronic's spinal fusion product shown to be harmful in bold review by medical journal and its Stanford editors". Inside Stanford Medicine (Stanford School of Medicine). Retrieved 2012-06-25.
↑ Carragee EJ, Hurwitz EL, Weiner BK (June 2011). "A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned" (PDF). Spine J 11 (6): 471–91. doi:10.1016/j.spinee.2011.04.023. PMID 21729796.

External links

BMPedia - the Bone Morphogenetic Protein Wiki
bone morphogenetic protein 2 at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery

1es7: COMPLEX BETWEEN BMP-2 AND TWO BMP RECEPTOR IA ECTODOMAINS

1reu: Structure of the bone morphogenetic protein 2 mutant L51P

1rew: Structural refinement of the complex of bone morphogenetic protein 2 and its type IA receptor

2goo: Ternary Complex of BMP-2 bound to BMPR-Ia-ECD and ActRII-ECD

2h62: Crystal structure of a ternary ligand-receptor complex of BMP-2

2h64: Crystal structure of a ternary ligand-receptor complex of BMP-2

3bmp: HUMAN BONE MORPHOGENETIC PROTEIN-2 (BMP-2)

Cell signaling: TGF beta signaling pathway

TGF beta superfamily of ligands

TGF beta family	TGF-β1 TGF-β2 TGF-β3

Bone morphogenetic proteins	BMP2 BMP3 BMP4 BMP5 BMP6 BMP7 BMP8a BMP8b BMP10 BMP15

Growth differentiation factors	GDF1 GDF2 GDF3 GDF5 GDF6 GDF7 Myostatin/GDF8 GDF9 GDF10 GDF11 GDF15

Other	Activin and inhibin Anti-müllerian hormone Nodal

TGF beta receptors
(Activin, BMP)

TGFBR1:	Activin type 1 receptors ACVR1 ACVR1B ACVR1C ACVRL1 BMPR1 BMPR1A BMPR1B

TGFBR2:	Activin type 2 receptors ACVR2A ACVR2B AMHR2 BMPR2

TGFBR3:	betaglycan

Transducers/SMAD

Ligand inhibitors

Coreceptors

BAMBI
Cripto

Other

SARA

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