BMP2

BMP2
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

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

Identifikatori
AliasiBMP2
Vanjski ID-jeviOMIM: 112261 MGI: 88177 HomoloGene: 926 GeneCards: BMP2
Lokacija gena (čovjek)
Hromosom 20 (čovjek)
Hrom.Hromosom 20 (čovjek)[1]
Hromosom 20 (čovjek)
Genomska lokacija za BMP2
Genomska lokacija za BMP2
Bend20p12.3Početak6,767,686 bp[1]
Kraj6,780,246 bp[1]
Lokacija gena (miš)
Hromosom 2 (miš)
Hrom.Hromosom 2 (miš)[2]
Hromosom 2 (miš)
Genomska lokacija za BMP2
Genomska lokacija za BMP2
Bend2 F2|2 65.21 cMPočetak133,394,079 bp[2]
Kraj133,404,805 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• signaling receptor binding
• cytokine activity
• co-receptor binding
• phosphatase activator activity
• growth factor activity
• BMP receptor binding
• GO:0001948, GO:0016582 vezivanje za proteine
• NAD-retinol dehydrogenase activity
• SMAD binding
• protein heterodimerization activity
• transforming growth factor beta receptor binding
Ćelijska komponenta• extracellular region
• cell surface
• BMP receptor complex
• Vanćelijsko
• intracellular membrane-bounded organelle
Biološki proces• skeletal system development
• positive regulation of Wnt signaling pathway by BMP signaling pathway
• positive regulation of protein phosphorylation
• 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 population proliferation
• positive regulation of p38MAPK cascade
• pathway-restricted SMAD protein phosphorylation
• cell fate commitment
• GO:0009373 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
• GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
• positive regulation of Wnt signaling pathway
• development of the heart
• 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
• Ćelijska diferencijacija
• chondrocyte differentiation
• corticotropin hormone secreting cell differentiation
• positive regulation of astrocyte differentiation
• positive regulation of bone mineralization
• GO:1904579 cellular response to organic cyclic compound
• positive regulation of ossification
• GO:1901227 negative regulation of transcription by RNA polymerase II
• 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
• protein destabilization
• embryonic heart tube anterior/posterior pattern specification
• osteoblast differentiation
• epithelial to mesenchymal transition
• positive regulation of protein binding
• GO:0045996 negative regulation of transcription, DNA-templated
• positive regulation of odontogenesis
• GO:0007329 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
• GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
• cardiac epithelial to mesenchymal transition
• positive regulation of pri-miRNA transcription by RNA polymerase II
• GO:1901313 positive regulation of gene expression
• BMP signaling pathway
• cardiac muscle cell differentiation
• cell development
• regulation of signaling receptor activity
• negative regulation of gene expression
• response to bacterium
• regulation of apoptotic process
• regulation of MAPK cascade
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

650

12156

Ensembl

ENSG00000125845

ENSMUSG00000027358

UniProt

P12643

P21274

RefSeq (mRNK)

NM_001200

NM_007553

RefSeq (bjelančevina)

NP_001191

NP_031579

Lokacija (UCSC)Chr 20: 6.77 – 6.78 MbChr 2: 133.39 – 133.4 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Protein 2 koštane morfogeneze ili BMP-2 pripada superporodici TGF-β proteina.[5]

Funkcija

BMP-2 kao i drugi protein morfogeneze kosti,[6] ima važnu ulogu u razvoju kostiju i hrskavice. Uključen je u put ježa, beta signalnog puta TGF i u citokinskim interakcijama receptora citokina. Također je uključen u diferencijaciju srčanih ćelija iz epitelne u mezenhimsku tranziciju.

Kao i mnogi drugi proteini iz porodice BMP, dokazano je da BMP-2 snažno inducira diferencijaciju osteoblasta u različitim tipovima ćelija.[7]

BMP-2 može biti uključen u adipogenezu bijelog masnog tliva[8][9] i može imati metaboličke efekte.[8][9]

Interakcije

Pokazalo se da protein 2 morfogeneze kosti ima interakcije sa BMPR1A.[10][11][12][13]

Klinička upotreba i komplikacije

Pokazalo se da protein 2morfogeneze kosti stimulira proizvodnju kostiju.[14][15] Rekombinantna ljudska bjelančevina (rhBMP-2) već je dostupna za ortopedsku upotrebu u Sjedinjenim Državama.[16] Implantacija BMP-2 obavlja se upotrebom različitih biomaterijalnih nosača ("metali, keramika, polimeri i kompoziti "[17]) i sistemi za isporuku ("hidrogel, mikrosfera, nanočestice i vlakna"[17]). Iako se koristi prvenstveno u ortopedskim zahvatima poput kičmene fuzije,[18][19] BMP-2 se također pronašao u oblasti stomatologije.[20][21][22]

Upotreba dvojakih konusnih fuzijskih kafeza i rekombinantnog proteina morfogeneze ljudske kosti na upijajućoj kolagenskoj spužvi dobijena je i održavala međupršljenska kičmena fuzija, poboljšani klinički ishodi i smanjeni bolovi nakon artrodeze slabinskog diska u prednjem dijelu slabinske kosti. Kao pomoćni sastojak alotransplanta kostiju ili kao zamjena za ubrani autotransplantat, čini se da proteini morfogeneze kostiju (BMP) poboljšavaju stopu fuzije nakon kičmene artrodeze i na životinjskim modelima i na ljudima, istovremeno smanjujući prethodno morbiditet na donatorskom mjestu povezan s takvim procedurama.[19]

Studija objavljena 2011. zabilježila je "izvještaje o čestim i povremeno katastrofalnim komplikacijama povezanim s upotrebom [BMP-2] u operacijama kičmene fuzije", s nivoom rizika daleko većim od procjena zabilježenih u ranijim studijama.[23][24] Dodatni pregled BMP-2 i njegovih uobičajenih sistema za isporuku Agrawala i Sinhe početkom 2016. pokazao je kako "problemi poput ektopskog rasta, manjeg dostavljanja proteina [i] inaktivacija proteina" otkrivaju daljnju potrebu "za modifikacijom dostupnim sistemima nosača kao i istraživanje drugih biomaterijala sa željenim svojstvima."[17]

Reference

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000125845 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027358 - Ensembl, maj 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. PMID 2376592. Arhivirano s originala, 9. 5. 2005. Pristupljeno 1. 5. 2021.
  6. ^ Chen D, Zhao M, Mundy GR (decembar 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. ^ a b Jin 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. ^ a b Blázquez-Medela AM, Jumabay M, Boström KI (januar 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 (februar 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.
  12. ^ Kirsch T, Nickel J, Sebald W (juli 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 (mart 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 (novembar 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 (maj 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.
  17. ^ 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 (4): 904–925. doi:10.1002/jbm.b.33599. PMID 26728994.
  18. ^ Burkus JK, Gornet MF, Schuler TC, Kleeman TJ, Zdeblick TA (maj 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. ^ 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): 1–6. doi:10.3171/foc.2001.10.4.4. PMID 16732630.
  20. ^ Allegrini S, Yoshimoto M, Salles MB, König B (februar 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 (decembar 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.
  22. ^ Schliephake H, Aref A, Scharnweber D, Bierbaum S, Roessler S, Sewing A (oktobar 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.
  23. ^ Richter R (28. 6. 2011). "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. Arhivirano s originala, 23. 4. 2012. Pristupljeno 25. 6. 2012.
  24. ^ Carragee EJ, Hurwitz EL, Weiner BK (juni 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. Arhivirano s originala (PDF), 10. 11. 2011.

Dopunska literatura

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

Vanjski linkovi

Šablon:Beta signalizacija TGF Šablon:Superfamilijski modulatori TGFβ receptora

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