Bone morphogenetic protein 7


Bone morphogenetic protein 7
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.
Identifiers
Symbol BMP7
External IDs OMIM112267 MGI103302 HomoloGene20410 GeneCards: BMP7 Gene
Orthologs
Species Human Mouse
Entrez 655 12162
Ensembl ENSG00000101144 ENSMUSG00000008999
UniProt P18075 P23359
RefSeq (mRNA) NM_001719 NM_007557
RefSeq (protein) NP_001710 NP_031583
Location (UCSC) Chr 20:
55.18 – 55.28 Mb
Chr 2:
172.7 – 172.77 Mb
PubMed search [1] [2]

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]

Contents

Function

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

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

Human recombinant BMP7 has surgical uses and is marketed under the brand name OP1 (sold by 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]

BMP7 also has the potential for treatment of chronic kidney disease.[7][8]

BMP7 administration has been proposed as a possible treatment for human infertility due to poor response to FSH treatment.[9]

Promotion of brown fat

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.[10][11]

References

  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. 
  2. ^ 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. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=149146. 
  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. 
  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. 
  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]" (in German). Unfallchirurg 110 (11): 931–8. doi:10.1007/s00113-007-1347-y. PMID 17989951. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ Jha A (2008-08-21). "Obesity: Scientists identify protein that promotes fat-burning". Science. guardian.co.uk. http://www.guardian.co.uk/science/2008/aug/21/brown.fat.obesity. Retrieved 2008-09-03. 
  11. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2745972. 

Further reading

External links


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