BMP2

BMP2
Dostupne strukture
PDB	Pretraga 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
Aliasi	BMP2
Vanjski ID-jevi	OMIM: 112261 MGI: 88177 HomoloGene: 926 GeneCards: BMP2
Lokacija gena (čovjek)
Hrom.	Hromosom 20 (čovjek)
Kraj	6,780,246 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	133,404,805 bp
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; • 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; • 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
	650
	12156
	ENSG00000125845
	ENSMUSG00000027358
	P12643
	P21274
	NM_001200
	NM_007553
	NP_001191
	NP_031579
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/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. 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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000125845 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027358 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ 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.
^ ^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.
^ ^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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^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.
^ 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.
^ ^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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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

bone morphogenetic protein 2 na US National Library of Medicine Medical Subject Headings (MeSH)
Lokacija ljudskog genoma BMP2 i stranica sa detaljima o genu BMP2 u UCSC Genome Browseru.

Šablon:Beta signalizacija TGF Šablon:Superfamilijski modulatori TGFβ receptora

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000125845 - Ensembl, maj 2017

[refGRCm38Ensembl-2] 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.

[pmid2376592-5] 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.

[pmid15621726-6] 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.

[pmid12168799-7] 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.

[:0-8] 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.

[:1-9] 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.

[pmid11263668-10] 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.

[pmid10692589-11] 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.

[pmid10880444-12] 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.

[pmid10712517-13] 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.

[urist1965-14] 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.

[pmid14623404-15] 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.

[pmid15155165-16] 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.

[AgrawalARev16-17] 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.

[pmid19411467-18] 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.

[pmid16732630-19] 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.

[pmid14737759-20] 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.

[pmid17092225-21] 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.

[pmid16164462-22] 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.

[pmid21729796-24] 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.

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