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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/11/15 19:45:51」(JST)

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For the portable synthesizer, see Teenage Engineering OP-1.

Bone morphogenetic protein 7 or BMP7 (also known as osteogenic protein-1 or OP-1) is a protein that in humans is encoded by the BMP7 gene.^[1]

Function[edit]

The protein encoded by this gene is a member of the TGF-β superfamily. Like other members of the bone morphogenetic protein family of proteins, it plays a key role in the transformation of mesenchymal cells into bone and cartilage. It is inhibited by noggin and a similar protein, chordin, which are expressed in the Spemann-Mangold Organizer. BMP7 may be involved in bone homeostasis. It is expressed in the brain, kidneys and bladder.^[2]

BMP7 induces the phosphorylation of SMAD1 and SMAD5, which in turn induce transcription of numerous osteogenic genes.^[3] It has been demonstrated that BMP7 treatment is sufficient to induce all of the genetic markers of osteoblast differentiation in many cell types.^[2]

Role in vertebrate development[edit]

BMP7 has been discovered to be crucial in the determination of ventral-dorsal organization in zebrafish. BMP7 causes the expression of ventral phenotypes while its complete inhibition creates a dorsal phenotype. Moreover, BMP7 is eventually partially "turned off" in embryonic development in order to create the dorsal parts of the organism.^[4]

In many early developmental experiments using zebrafish, scientists used caBMPR (constitutively active) and tBMP (truncated receptor) to determine the effect of BMP7 in embryogensis. They found that the constitutively active, which causes BMP to be expressed everywhere creates a ventralized phenotype, whereas truncated, dorsalized.

Therapeutic application[edit]

See also: Bone morphogenetic protein#Clinical uses

Human recombinant BMP7 has surgical uses and is marketed under the brand name OP1 (sold by Olympus, who bought it from Stryker). It can be used to aid in the fusion of vertebral bodies to prevent neurologic trauma.^[5] Also in the treatment of tibial non-union, frequently in cases where a bone graft has failed.^[6] rhBMP-2 is much more widely used clinically because it helps grow bone better than rhBMP-7 and other BMPs.^[7]

BMP7 also has the potential for treatment of chronic kidney disease.^[8]^[9]

BMP7 administration has been proposed as a possible treatment for human infertility due to poor response to FSH treatment.^[10]

Promotion of brown fat[edit]

It was discovered that mice injected with BMP7 increased their production of "good" brown fat cells, while keeping their levels of the normal white fat cells constant. A BMP7 therapy for obesity in humans may be developed as a result.^[11]^[12]

References[edit]

^ Hahn GV, Cohen RB, Wozney JM, Levitz CL, Shore EM, Zasloff MA, Kaplan FS (November 1992). "A bone morphogenetic protein subfamily: chromosomal localization of human genes for BMP5, BMP6, and BMP7". Genomics 14 (3): 759–62. doi:10.1016/S0888-7543(05)80181-8. PMID 1427904.
^ ^a ^b Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic proteins". Growth Factors 22 (4): 233–41. doi:10.1080/08977190412331279890. PMID 15621726.
^ Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". EMBO J. 20 (15): 4132–42. doi:10.1093/emboj/20.15.4132. PMC 149146. PMID 11483516.
^ Myers DC, Sepich DS, Solnica-Krezel L (March 2002). "Bmp activity gradient regulates convergent extension during zebrafish gastrulation". Dev. Biol. 243 (1): 81–98. doi:10.1006/dbio.2001.0523. PMID 11846479.
^ Vaccaro AR, Whang PG, Patel T, Phillips FM, Anderson DG, Albert TJ, Hilibrand AS, Brower RS, Kurd MF, Appannagari A, Patel M, Fischgrund JS (2008). "The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study". Spine J 8 (3): 457–65. doi:10.1016/j.spinee.2007.03.012. PMID 17588821.
^ Zimmermann G, Müller U, Löffler C, Wentzensen A, Moghaddam A (November 2007). "[Therapeutic outcome in tibial pseudarthrosis: bone morphogenetic protein 7 (BMP-7) versus autologous bone grafting for tibial fractures]". Unfallchirurg (in German) 110 (11): 931–8. doi:10.1007/s00113-007-1347-y. PMID 17989951.
^ Even J, Eskander M, Kang J (2012). "Bone morphogenetic protein in spine surgery: current and future uses". J Am Acad Orthop Surg (20): 547–52. PMID 22941797.
^ Gould SE, Day M, Jones SS, Dorai H (January 2002). "BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells". Kidney Int. 61 (1): 51–60. doi:10.1046/j.1523-1755.2002.00103.x. PMID 11786084.
^ González EA, Lund RJ, Martin KJ, McCartney JE, Tondravi MM, Sampath TK, Hruska KA (April 2002). "Treatment of a murine model of high-turnover renal osteodystrophy by exogenous BMP-7". Kidney Int. 61 (4): 1322–31. doi:10.1046/j.1523-1755.2002.00258.x. PMID 11918739.
^ Shi J, Yoshino O, Osuga Y, Nishii O, Yano T, Taketani Y (March 2010). "Bone morphogenetic protein 7 (BMP-7) increases the expression of follicle-stimulating hormone (FSH) receptor in human granulosa cells". Fertil. Steril. 93 (4): 1273–9. doi:10.1016/j.fertnstert.2008.11.014. PMID 19108831.
^ Jha A (2008-08-21). "Obesity: Scientists identify protein that promotes fat-burning". Science. guardian.co.uk. Retrieved 2008-09-03.
^ Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR (August 2008). "New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure". Nature 454 (7207): 1000–4. doi:10.1038/nature07221. PMC 2745972. PMID 18719589.

External links[edit]

bone morphogenetic protein 7 at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 慢性C型肝炎ウイルス感染の治療のための標準的なインターフェロンアルファの作用機序
および有効性 mechanism of action and efficacy of standard interferon alfa for the treatment of chronic hepatitis c virus infection
2. 慢性腎疾患における貧血のマネージメントのためのダルベポエチンアルファ darbepoetin alfa for the management of anemia in chronic kidney disease
3. インターフェロンα + リバビリン療法関連の神経精神学的副作用：治療および予防 neuropsychiatric side effects associated with interferon alfa plus ribavirin therapy treatment and prevention
4. 慢性C型肝炎ウイルス感染の治療のためのリバビリンの作用機序および有効性 mechanism of action and efficacy of ribavirin for the treatment of chronic hepatitis c virus infection
5. 慢性C型肝炎ウイルス感染の治療のためのペグインターフェロンの作用機序および
有効性 mechanism of action and efficacy of peginterferon for the treatment of chronic hepatitis c virus infection

English Journal

Clinical effectiveness of Osigraft in long-bones non-unions.

Calori GM1, Colombo M2, Bucci M2, Mazza EL2, Fadigati P2, Mazzola S2.
Injury.Injury.2015 Dec;46 Suppl 8:S55-64. doi: 10.1016/S0020-1383(15)30056-5.
Current evidence, based primarily on case series, suggest that the eptotermin alfa (recombinant bone morphogenetic protein-7 (rhBM-7)), which is commercialized as Osigraft with an indication for tibial non-union, used in monotherapy or polytherapy, is a safe and effective therapy for long bones non-
PMID 26747920

Cost effectiveness of tibial nonunion treatment: A comparison between rhBMP-7 and autologous bone graft in two Italian centres.

Giorgio Calori M1, Capanna R, Colombo M, De Biase P, O'Sullivan C, Cartareggia V, Conti C.
Injury.Injury.2013 Dec;44(12):1871-9. doi: 10.1016/j.injury.2013.08.012. Epub 2013 Aug 30.
Current evidences show that recombinant human bone morphogenetic protein 7 (rhBMP-7, eptotermin alfa) can be considered an effective alternative to autologous bone graft (ABG) in the treatment of tibial nonunions. Few studies, so far, have analysed the costs of treating tibial nonunions with either
PMID 24074829

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「alfa」

Bone morphogenetic protein 7
	; Crystal structure of Bone Morphogenetic Protein-7 (BMP-7) in complex with the secreted antagonist Noggin. PDB rendering based on 1m4u.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1BMP, 1LX5, 1LXI, 1M4U
Identifiers
Symbols	BMP7; OP-1
External IDs	OMIM: 112267 MGI: 103302 HomoloGene: 20410 GeneCards: BMP7 Gene
Gene Ontology
Molecular function	• cytokine activity; • protein binding; • growth factor activity;
Cellular component	• extracellular region; • extracellular space;
Biological process	• skeletal system development; • ossification; • metanephros development; • ureteric bud development; • mesoderm formation; • mesonephros development; • epithelial to mesenchymal transition; • axon guidance; • embryonic pattern specification; • negative regulation of striated muscle cell apoptotic process; • positive regulation of peptidyl-threonine phosphorylation; • positive regulation of pathway-restricted SMAD protein phosphorylation; • dendrite development; • extracellular matrix organization; • embryonic limb morphogenesis; • positive regulation of bone mineralization; • BMP signaling pathway; • epithelial cell differentiation; • negative regulation of NF-kappaB transcription factor activity; • positive regulation of heterotypic cell-cell adhesion; • protein localization to nucleus; • growth; • negative regulation of phosphorylation; • negative regulation of NF-kappaB import into nucleus; • odontogenesis of dentin-containing tooth; • positive regulation of apoptotic process; • steroid hormone mediated signaling pathway; • negative regulation of MAP kinase activity; • negative regulation of neuron differentiation; • positive regulation of neuron differentiation; • positive regulation of osteoblast differentiation; • negative regulation of Notch signaling pathway; • negative regulation of cell cycle; • negative regulation of mitosis; • negative regulation of transcription, DNA-dependent; • positive regulation of transcription, DNA-dependent; • positive regulation of transcription from RNA polymerase II promoter; • embryonic camera-type eye morphogenesis; • branching morphogenesis of an epithelial tube; • mesenchymal cell differentiation; • neuron projection morphogenesis; • negative regulation of neurogenesis; • cartilage development; • embryonic skeletal joint morphogenesis; • regulation of pathway-restricted SMAD protein phosphorylation; • SMAD protein signal transduction; • branching involved in salivary gland morphogenesis; • mesenchyme development; • negative regulation of cell death; • negative regulation of prostatic bud formation; • regulation of branching involved in prostate gland morphogenesis; • monocyte aggregation; • cellular response to hypoxia; • negative regulation of mesenchymal cell apoptotic process involved in nephron morphogenesis; • negative regulation of glomerular mesangial cell proliferation; • metanephric mesenchyme morphogenesis; • nephrogenic mesenchyme morphogenesis; • metanephric mesenchymal cell proliferation involved in metanephros development; • positive regulation of dendrite development; • positive regulation of hyaluranon cable assembly; • regulation of removal of superoxide radicals;
	Sources: Amigo / QuickGO
Orthologs
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α、アルファ

関: alpha

[pmid1427904-1] Hahn GV, Cohen RB, Wozney JM, Levitz CL, Shore EM, Zasloff MA, Kaplan FS (November 1992). "A bone morphogenetic protein subfamily: chromosomal localization of human genes for BMP5, BMP6, and BMP7". Genomics 14 (3): 759–62. doi:10.1016/S0888-7543(05)80181-8. PMID 1427904.

[pmid15621726-2] Chen D, Zhao M, Mundy GR (December 2004). "Bone morphogenetic proteins". Growth Factors 22 (4): 233–41. doi:10.1080/08977190412331279890. PMID 15621726.

[pmid11483516-3] Itoh F, Asao H, Sugamura K, Heldin CH, ten Dijke P, Itoh S (August 2001). "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". EMBO J. 20 (15): 4132–42. doi:10.1093/emboj/20.15.4132. PMC 149146. PMID 11483516.

[pmid11846479-4] Myers DC, Sepich DS, Solnica-Krezel L (March 2002). "Bmp activity gradient regulates convergent extension during zebrafish gastrulation". Dev. Biol. 243 (1): 81–98. doi:10.1006/dbio.2001.0523. PMID 11846479.

[pmid17588821-5] Vaccaro AR, Whang PG, Patel T, Phillips FM, Anderson DG, Albert TJ, Hilibrand AS, Brower RS, Kurd MF, Appannagari A, Patel M, Fischgrund JS (2008). "The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study". Spine J 8 (3): 457–65. doi:10.1016/j.spinee.2007.03.012. PMID 17588821.

[pmid17989951-6] Zimmermann G, Müller U, Löffler C, Wentzensen A, Moghaddam A (November 2007). "[Therapeutic outcome in tibial pseudarthrosis: bone morphogenetic protein 7 (BMP-7) versus autologous bone grafting for tibial fractures]". Unfallchirurg (in German) 110 (11): 931–8. doi:10.1007/s00113-007-1347-y. PMID 17989951.

[Even-7] Even J, Eskander M, Kang J (2012). "Bone morphogenetic protein in spine surgery: current and future uses". J Am Acad Orthop Surg (20): 547–52. PMID 22941797.

[pmid11786084-8] Gould SE, Day M, Jones SS, Dorai H (January 2002). "BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells". Kidney Int. 61 (1): 51–60. doi:10.1046/j.1523-1755.2002.00103.x. PMID 11786084.

[pmid11918739-9] González EA, Lund RJ, Martin KJ, McCartney JE, Tondravi MM, Sampath TK, Hruska KA (April 2002). "Treatment of a murine model of high-turnover renal osteodystrophy by exogenous BMP-7". Kidney Int. 61 (4): 1322–31. doi:10.1046/j.1523-1755.2002.00258.x. PMID 11918739.

[pmid19108831-10] Shi J, Yoshino O, Osuga Y, Nishii O, Yano T, Taketani Y (March 2010). "Bone morphogenetic protein 7 (BMP-7) increases the expression of follicle-stimulating hormone (FSH) receptor in human granulosa cells". Fertil. Steril. 93 (4): 1273–9. doi:10.1016/j.fertnstert.2008.11.014. PMID 19108831.

[urlObesity:_Scientists_identify_protein_that_promotes_fat-burning_.7C_Science_.7C-11] Jha A (2008-08-21). "Obesity: Scientists identify protein that promotes fat-burning". Science. guardian.co.uk. Retrieved 2008-09-03.

[pmid18719589-12] Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR (August 2008). "New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure". Nature 454 (7207): 1000–4. doi:10.1038/nature07221. PMC 2745972. PMID 18719589.

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eptotermin alfa