Bone morphogenetic protein 2

From Wikipedia, the free encyclopedia
Jump to: navigation, search
BMP2
BMP2.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases BMP2, BDA2, BMP2A, bone morphogenetic protein 2
External IDs OMIM: 112261 MGI: 88177 HomoloGene: 926 GeneCards: 650
Genetically Related Diseases
Disease Name References
obesity
RNA expression pattern
PBB GE BMP2 205289 at tn.png

PBB GE BMP2 205290 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
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.[1]

Function[edit]

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[edit]

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

Clinical use and complications[edit]

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[edit]

  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. ^ a b c 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. ^ a b 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. ^ a b 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[edit]

  • 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[edit]