Bone morphogenetic protein 2

Bone morphogenetic protein 2
PDB rendering based on 3bmp.
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
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
Entrez	650	12156
Ensembl	ENSG00000125845	ENSMUSG00000027358
UniProt	P12643	P21274
RefSeq (mRNA)	NM_001200	NM_007553
RefSeq (protein)	NP_001191	NP_031579
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 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.^[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][9] Recombinant human protein (rhBMP-2) is currently available for orthopaedic usage in the United States.^[10] Implantation of BMP-2 is performed using a variety of biomaterial carriers ("metals, ceramics, polymers, and composites"^[11]) and delivery systems ("hydrogel, microsphere, nanoparticles, and fibers"^[11]). While used primarily in orthopedic procedures such as spinal fusion,^[12][13] BMP-2 has also found its way into the field of dentistry.^[14][15][16]

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.^[12] 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.^[13]

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.^[17][18] 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."^[11]

References

1. 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.
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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Urist MR (1965). "Bone: formation by autoinduction". Science 150 (3698): 893–9. doi:10.1126/science.150.3698.893. PMID 5319761.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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)