Bone morphogenetic protein 2

Bone morphogenetic protein 2
PDB rendering based on 3bmp.
Available structures PDB 1ES7, 1REU, 1REW, 2H62, 2H64, 2QJ9, 2QJA, 2QJB, 3BK3, 3BMP
Identifiers
Symbols	BMP2; BMP2A
External IDs	OMIM: 112261 MGI: 88177 HomoloGene: 926 GeneCards: BMP2 Gene
Gene Ontology Molecular function • transmembrane receptor protein serine/threonine kinase activity • retinol dehydrogenase activity • receptor binding • cytokine activity • transforming growth factor beta receptor binding • protein binding • growth factor activity • activin receptor activity, type II • phosphatase activator activity • protein domain specific binding • protein homodimerization activity • SMAD binding • protein heterodimerization activity • BMP receptor binding Cellular component • extracellular region • extracellular region • extracellular space • cytoplasm • membrane-bounded vesicle • protein complex Biological process • negative regulation of transcription from RNA polymerase II promoter • 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 • BMP signaling pathway involved in heart induction • atrioventricular valve morphogenesis • endocardial cushion morphogenesis • regulation of transcription, DNA-dependent • inflammatory response • Notch signaling pathway • cell-cell signaling • negative regulation of cell proliferation • response to mechanical stimulus • embryo development • organ morphogenesis • positive regulation of gene expression • positive regulation of epithelial to mesenchymal transition • positive regulation of pathway-restricted SMAD protein phosphorylation • positive regulation of pathway-restricted SMAD protein phosphorylation • positive regulation of phosphatase activity • telencephalon development • telencephalon regionalization • positive regulation of bone mineralization • BMP signaling pathway • BMP signaling pathway • BMP signaling pathway • protein destabilization • response to retinoic acid • cardiac cell differentiation • cardiac cell differentiation • embryonic heart tube anterior/posterior pattern formation • bone mineralization involved in bone maturation • growth • positive regulation of odontogenesis • regulation of odontogenesis of dentine-containing tooth • ovulation cycle • positive regulation of apoptosis • cell fate commitment • positive regulation of neuron differentiation • positive regulation of osteoblast differentiation • positive regulation of ossification • negative regulation of cell cycle • negative regulation of transcription, DNA-dependent • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • positive regulation of astrocyte differentiation • mesenchymal cell differentiation • positive regulation of neurogenesis • cardiac muscle tissue morphogenesis • 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 • positive regulation of WNT receptor signaling pathway by BMP signaling pathway • positive regulation of cartilage development • cellular response to growth factor stimulus • cellular response to organic cyclic compound Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	650	12156
Ensembl	ENSG00000125845	ENSMUSG00000027358
UniProt	P12643	Q3V1I4
RefSeq (mRNA)	NM_001200.2	NM_007553.2
RefSeq (protein)	NP_001191.1	NP_031579.2
Location (UCSC)	Chr 20: 6.75 – 6.76 Mb	Chr 2: 133.38 – 133.39 Mb
PubMed search	[1]	[2]

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]

Medical uses

Bone morphogenetic protein 2 is shown to stimulate the production of bone.^[4] Recombinant human protein (rhBMP-2) is currently available for orthopaedic usage in the United States.^[5] 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.^[6]

Bone morphogenetic protein 2 has also found its way into the field of Dentistry. Oral Surgery and Implant Dentistry in particular have benefited dramatically from commercially available BMP-2.^[7][8][9] 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.^[10] 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.^[11]

Interactions

Bone morphogenetic protein 2 has been shown to interact with BMPR1A.^{[12][13][14][15]}

References

1. ^ Sampath TK, Coughlin JE, Whetstone RM, Banach D, Corbett C, Ridge RJ, Ozkaynak E, Oppermann H, Rueger DC (5 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. http://www.jbc.org/cgi/content/abstract/265/22/13198. 
2. ^ Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic proteins". Growth Factors 22 (4): 233–41. doi:10.1080/08977190412331279890. PMID 15621726. 
3. ^ 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. http://www.hh.um.es/Abstracts/Vol_17/17_3/17_3_877.htm. 
4. ^ Urist, Marshall R. (1965). "Bone: formation by autoinduction". Science 12:150 (698): 893–899. doi:10.1126/science.150.3698.893. PMID 5319761. 
5. ^ 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. 
6. ^ 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. 
7. ^ 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. 
8. ^ 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. 
9. ^ 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. 
10. ^ 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. 
11. ^ Subach BR, Haid RW, Rodts GE, Kaiser MG (2001). "Bone morphogenetic protein in spinal fusion: overview and clinical update". Neurosurg Focus 10 (4): E3. PMID 16732630. 
12. ^ Nickel, J; Dreyer M K, Kirsch T, Sebald W (2001). "The crystal structure of the BMP-2:BMPR-IA complex and the generation of BMP-2 antagonists". The Journal of bone and joint surgery. American volume (United States) 83-A Suppl 1 (Pt 1): S7–14. ISSN 0021-9355. PMID 11263668. 
13. ^ Kirsch, T; Nickel J, Sebald W (Feb. 2000). "Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP-2". FEBS Lett. (NETHERLANDS) 468 (2-3): 215–9. doi:10.1016/S0014-5793(00)01214-X. ISSN 0014-5793. PMID 10692589. 
14. ^ Kirsch, T; Nickel J, Sebald W (Jul. 2000). "BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II". EMBO J. (ENGLAND) 19 (13): 3314–24. doi:10.1093/emboj/19.13.3314. ISSN 0261-4189. PMC 313944. PMID 10880444. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=313944. 
15. ^ Gilboa, L; Nohe A, Geissendörfer T, Sebald W, Henis Y I, Knaus P (Mar. 2000). "Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors". Mol. Biol. Cell (UNITED STATES) 11 (3): 1023–35. ISSN 1059-1524. PMC 14828. PMID 10712517. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=14828. 

Further reading

• 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.". The Journal of bone and joint surgery. American volume 83-A Suppl 1 (Pt 1): S7–14. PMID 11263668. 
• Kawamura C, Kizaki M, Ikeda Y (2003). "Bone morphogenetic protein (BMP)-2 induces apoptosis in human myeloma cells.". Leuk. Lymphoma 43 (3): 635–9. doi:10.1080/10428190290012182. PMID 12002771. 
• Marie PJ, Debiais F, Haÿ E (2003). "Regulation of human cranial osteoblast phenotype by FGF-2, FGFR-2 and BMP-2 signaling.". Histol. Histopathol. 17 (3): 877–85. PMID 12168799. 

External links

• BMPedia - the Bone Morphogenetic Protein Wiki
• MeSH bone+morphogenetic+protein+2