BMP2

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BMP2
BMP2.png
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 cMPočetak133,552,159 bp[2]
Kraj133,562,885 bp[2]
Obrazac RNK ekspresije
PBB GE BMP2 205290 s at fs.png

PBB GE BMP2 205289 at fs.png
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 protein binding
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
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
positive regulation of transcription, DNA-templated
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
Ćelijska diferencijacija
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 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
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
positive regulation of transcription by RNA polymerase II
cardiac epithelial to mesenchymal transition
positive regulation of pri-miRNA transcription by RNA polymerase II
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
Ensembl
UniProt
RefSeq (mRNK)

NM_001200

NM_007553

RefSeq (bjelančevina)

NP_001191

NP_031579

Lokacija (UCSC)Chr 20: 6.77 – 6.78 MbChr 2: 133.55 – 133.56 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[uredi | uredi izvor]

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[uredi | uredi izvor]

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

Klinička upotreba i komplikacije[uredi | uredi izvor]

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. godine 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. godine 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[uredi | uredi izvor]

  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[uredi | uredi izvor]

  • 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[uredi | uredi izvor]

Šablon:PDB Gallery Šablon:Beta signalizacija TGF Šablon:Superfamilijski modulatori TGFβ receptora