Bone morphogenetic protein 2

BMP2
Available structures PDB 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
Aliases	BMP2, BDA2, BMP2A, bone morphogenetic protein 2
External IDs	OMIM: 112261 MGI: 88177 HomoloGene: 926 GeneCards: BMP2
Genetically Related Diseases
obesity[1]
Gene ontology Molecular function • receptor binding • cytokine activity • co-receptor binding • phosphatase activator activity • growth factor activity • BMP receptor binding • protein binding • retinol dehydrogenase activity • SMAD binding • protein heterodimerization activity • transforming growth factor beta receptor binding Cellular component • extracellular region • extracellular space • cell surface • BMP receptor complex Biological process • skeletal system development • positive regulation of Wnt signaling pathway by BMP signaling pathway • positive regulation of protein phosphorylation • embryo development • mesenchyme development • negative regulation of cell cycle • odontogenesis of dentin-containing tooth • telencephalon regionalization • protein phosphorylation • atrioventricular valve morphogenesis • proteoglycan metabolic process • mesenchymal cell differentiation • pericardium development • positive regulation of ERK1 and ERK2 cascade • BMP signaling pathway involved in heart induction • animal organ morphogenesis • inner ear development • cardiocyte differentiation • negative regulation of canonical Wnt signaling pathway • negative regulation of cell proliferation • positive regulation of p38MAPK cascade • pathway-restricted SMAD protein phosphorylation • cell fate commitment • regulation of transcription, DNA-templated • SMAD protein signal transduction • ossification • in utero embryonic development • mesenchymal cell proliferation involved in ureteric bud development • regulation of odontogenesis of dentin-containing tooth • negative regulation of gene expression • positive regulation of transcription, DNA-templated • growth • positive regulation of Wnt signaling pathway • heart development • telencephalon development • branching involved in ureteric bud morphogenesis • negative regulation of Wnt signaling pathway involved in heart development • cartilage development • bone mineralization involved in bone maturation • positive regulation of cartilage development • positive regulation of neuron differentiation • positive regulation of cell differentiation • thyroid-stimulating hormone-secreting cell differentiation • inflammatory response • positive regulation of fat cell differentiation • negative regulation of steroid biosynthetic process • positive regulation of MAPK cascade • Notch signaling pathway • bone mineralization • cell differentiation • chondrocyte differentiation • corticotropin hormone secreting cell differentiation • positive regulation of astrocyte differentiation • positive regulation of bone mineralization • cellular response to organic cyclic compound • positive regulation of ossification • negative regulation of transcription from RNA polymerase II promoter • positive regulation of epithelial to mesenchymal transition • positive regulation of phosphatase activity • negative regulation of calcium-independent cell-cell adhesion • positive regulation of osteoblast differentiation • activation of MAPK activity • protein destabilization • embryonic heart tube anterior/posterior pattern specification • osteoblast differentiation • epithelial to mesenchymal transition • positive regulation of protein binding • negative regulation of transcription, DNA-templated • positive regulation of odontogenesis • positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus • negative regulation of aldosterone biosynthetic process • positive regulation of osteoblast proliferation • response to hypoxia • positive regulation of endothelial cell proliferation • positive regulation of cell migration • negative regulation of cortisol biosynthetic process • cell-cell signaling • positive regulation of pathway-restricted SMAD protein phosphorylation • cellular response to growth factor stimulus • cellular response to BMP stimulus • cardiac muscle tissue morphogenesis • endocardial cushion morphogenesis • multicellular organism development • negative regulation of cardiac muscle cell differentiation • positive regulation of apoptotic process • negative regulation of insulin-like growth factor receptor signaling pathway • oxidation-reduction process • positive regulation of transcription from RNA polymerase II promoter • cardiac epithelial to mesenchymal transition • positive regulation of pri-miRNA transcription from RNA polymerase II promoter • positive regulation of gene expression • BMP signaling pathway • cardiac muscle cell differentiation Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	650	12156
Ensembl	ENSG00000125845	ENSMUSG00000027358
UniProt	P12643	P21274
RefSeq (mRNA)	NM_001200	NM_007553
RefSeq (protein)	NP_001191.1	NP_031579.2
Location (UCSC)	Chr 20: 6.77 – 6.78 Mb	Chr 2: 133.55 – 133.56 Mb
PubMed search	[2]	[3]
Wikidata

View/Edit Human

View/Edit Mouse

Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.^[4]

Function

BMP-2 like other bone morphogenetic proteins,^[5] 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 also involved 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.^[6]

Interactions

Bone morphogenetic protein 2 has been shown to interact with BMPR1A.^{[7][8][9][10]}

Clinical use and complications

Bone morphogenetic protein 2 is shown to stimulate the production of bone.^[11][12] Recombinant human protein (rhBMP-2) is currently available for orthopaedic usage in the United States.^[13] Implantation of BMP-2 is performed using a variety of biomaterial carriers ("metals, ceramics, polymers, and composites"^[14]) and delivery systems ("hydrogel, microsphere, nanoparticles, and fibers"^[14]). While used primarily in orthopedic procedures such as spinal fusion,^[15][16] BMP-2 has also found its way into the field of dentistry.^[17][18][19]

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.^[15] 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.^[16]

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.^[20][21] An additional review by Agrawal and Sinha of BMP-2 and its common delivery systems in early 2016 showed how "problems like ectopic growth, lesser protein delivery, [and] inactivation of the protein" reveal a further need "to modify the available carrier systems as well as explore other biomaterials with desired properties."^[14]

References

1. "Diseases that are genetically associated with BMP2 view/edit references on wikidata".
2. "Human PubMed Reference:".
3. "Mouse PubMed Reference:".
4. 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.
5. Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic proteins". Growth Factors. 22 (4): 233–41. doi:10.1080/08977190412331279890. PMID 15621726.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Urist MR (1965). "Bone: formation by autoinduction". Science. 150 (3698): 893–9. doi:10.1126/science.150.3698.893. PMID 5319761.
12. 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.
13. 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.
14. Agrawal, V; Sinha, M. (2016). "A review on carrier systems for bone morphogenetic protein-2". Journal of Biomedical Materials Research Part B: Applied Biomaterials. Early View. doi:10.1002/jbm.b.33599. PMID 26728994.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.

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". J Bone Joint Surg Am. 83-A Suppl 1 (Pt 1): S7–14. PMID 11263668.
• Kawamura C, Kizaki M, Ikeda Y (2002). "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 (2002). "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
• bone morphogenetic protein 2 at the US National Library of Medicine Medical Subject Headings (MeSH)