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Bone morphogenetic protein 2

From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
BMP2
Available structures
PDBOrtholog search:PDBeRCSB
List of PDB id codes

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

Identifiers
AliasesBMP2, BDA2, BMP2A, bone morphogenetic protein 2, SSFSC, SSFSC1
External IDsOMIM:112261;MGI:88177;HomoloGene:926;GeneCards:BMP2;OMA:BMP2 - orthologs
Gene location (Human)
Chromosome 20 (human)
Chr.Chromosome 20 (human)[1]
Chromosome 20 (human)
Genomic location for BMP2
Genomic location for BMP2
Band20p12.3Start6,767,686bp[1]
End6,780,246bp[1]
Gene location (Mouse)
Chromosome 2 (mouse)
Chr.Chromosome 2 (mouse)[2]
Chromosome 2 (mouse)
Genomic location for BMP2
Genomic location for BMP2
Band2 F2|2 65.21 cMStart133,394,079bp[2]
End133,404,805bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • cartilage tissue

  • pancreatic ductal cell

  • retinal pigment epithelium

  • mucosa of sigmoid colon

  • lower lobe of lung

  • pylorus

  • periodontal fiber

  • mucosa of urinary bladder

  • stromal cell of endometrium

  • glomerulus
Top expressed in
  • gastrula

  • transitional epithelium of urinary bladder

  • epithelium of stomach

  • left colon

  • ciliary body

  • mucous cell of stomach

  • Apical ectodermal ridge

  • sebaceous gland

  • retinal pigment epithelium

  • pyloric antrum
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo /QuickGO
Orthologs
SpeciesHumanMouse
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 MbChr 2: 133.39 – 133.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Bone morphogenetic protein 2 orBMP-2 belongs to theTGF-β superfamily ofproteins.[5]

Function

[edit]

BMP-2 like otherbone morphogenetic proteins,[6] plays an important role in the development of bone and cartilage. It is involved in thehedgehog pathway,TGF beta signaling pathway, and incytokine-cytokine receptor interaction. It is also involved in cardiac cell differentiation andepithelial to mesenchymal transition.

Like many other proteins from the BMP family, BMP-2 has been demonstrated to potently induceosteoblastdifferentiation in a variety of cell types.[7]

BMP-2 may be involved in white adipogenesis[8][9] and may have metabolic effects.[8][9]

Interactions

[edit]

Bone morphogenetic protein 2 has been shown tointeract withBMPR1A.[10][11][12][13]

Clinical use and complications

[edit]
See also:Bone morphogenetic protein § Clinical uses

Bone morphogenetic protein 2 is shown to stimulate the production of bone.[14][15]Recombinant human protein (rhBMP-2) is currently available fororthopaedic usage in theUnited States.[16] Implantation of BMP-2 is performed using a variety ofbiomaterial carriers ("metals, ceramics, polymers, and composites"[17]) and delivery systems ("hydrogel, microsphere, nanoparticles, and fibers"[17]). While used primarily in orthopedic procedures such as spinal fusion,[18][19] BMP-2 has also found its way into the field of dentistry.[20][21][22]

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.[18] 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.[19]

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.[23][24] 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."[17]

References

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000125845Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000027358Ensembl, May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^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.doi:10.1016/S0021-9258(19)38285-7.PMID 2376592.
  6. ^Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic proteins".Growth Factors.22 (4):233–41.doi:10.1080/08977190412331279890.PMID 15621726.S2CID 22932278.
  7. ^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.doi:10.14670/HH-17.877.PMID 12168799.
  8. ^abJin W, Takagi T, Kanesashi SN, Kurahashi T, Nomura T, Harada J, Ishii S (April 2006)."Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad proteins".Developmental Cell.10 (4):461–71.doi:10.1016/j.devcel.2006.02.016.PMID 16580992.
  9. ^abBlázquez-Medela AM, Jumabay M, Boström KI (January 2019)."Beyond the bone: Bone morphogenetic protein signaling in adipose tissue".Obesity Reviews.20 (5):648–658.doi:10.1111/obr.12822.PMC 6447448.PMID 30609449.
  10. ^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.
  11. ^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.Bibcode:2000FEBSL.468..215K.doi:10.1016/S0014-5793(00)01214-X.PMID 10692589.S2CID 30068719.
  12. ^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.
  13. ^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.
  14. ^Urist MR (1965). "Bone: formation by autoinduction".Science.150 (3698):893–9.Bibcode:1965Sci...150..893U.doi:10.1126/science.150.3698.893.PMID 5319761.S2CID 83951938.
  15. ^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.
  16. ^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.S2CID 45699304.
  17. ^abcAgrawal, 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 (4):904–925.doi:10.1002/jbm.b.33599.PMID 26728994.
  18. ^abBurkus 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.
  19. ^abSubach BR, Haid RW, Rodts GE, Kaiser MG (2001)."Bone morphogenetic protein in spinal fusion: overview and clinical update".Neurosurg Focus.10 (4):1–6.doi:10.3171/foc.2001.10.4.4.PMID 16732630.
  20. ^Allegrini S, Yoshimoto M, Salles MB, König B (February 2004)."Bone regeneration in rabbit sinus lifting associated with bovine BMP".Journal of Biomedical Materials Research Part B: Applied Biomaterials.68 (2):127–31.doi:10.1002/jbm.b.20006.PMID 14737759.
  21. ^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".Clinical Oral Implants Research.17 (6):666–72.doi:10.1111/j.1600-0501.2006.01214.x.PMID 17092225.
  22. ^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".Clinical Oral Implants Research.16 (5):563–9.doi:10.1111/j.1600-0501.2005.01143.x.PMID 16164462.
  23. ^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. Archived fromthe original on 2012-04-23. Retrieved2012-06-25.
  24. ^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. Archived fromthe original(PDF) on 2011-11-10.

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.S2CID 42810021.
  • 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.doi:10.14670/HH-17.877.PMID 12168799.

External links

[edit]
PDB gallery
  • 1es7: COMPLEX BETWEEN BMP-2 AND TWO BMP RECEPTOR IA ECTODOMAINS
    1es7: COMPLEX BETWEEN BMP-2 AND TWO BMP RECEPTOR IA ECTODOMAINS
  • 1reu: Structure of the bone morphogenetic protein 2 mutant L51P
    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
    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
    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
    2h62: Crystal structure of a ternary ligand-receptor complex of BMP-2
  • 2h64: 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)
    3bmp: HUMAN BONE MORPHOGENETIC PROTEIN-2 (BMP-2)
TGF beta superfamily of ligands
Ligand ofACVR orTGFBR
Ligand ofBMPR
TGF beta receptors
(Activin,BMP,family)
TGFBR1:
TGFBR2:
TGFBR3:
Transducers/SMAD
Ligand inhibitors
Coreceptors
Other
Type I
ALK1 (ACVRL1)
ALK2 (ACVR1A)
ALK3 (BMPR1A)
ALK4 (ACVR1B)
ALK5 (TGFβR1)
ALK6 (BMPR1B)
ALK7 (ACVR1C)
Type II
TGFβR2
BMPR2
ACVR2A (ACVR2)
ACVR2B
AMHR2 (AMHR)
Type III
TGFβR3 (β-glycan)
Unsorted
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