Bone morphogenetic protein 6 explained

Bone morphogenetic protein 6 is a protein that in humans is encoded by the BMP6 gene.^{[1] [2] [3]}

The protein encoded by this gene is a member of the TGFβ superfamily. Bone morphogenetic proteins are known for their ability to induce the growth of bone and cartilage. BMP6 is able to induce all osteogenic markers in mesenchymal stem cells.

The bone morphogenetic proteins (BMPs) are a family of secreted signaling molecules that can induce ectopic bone growth. BMPs are part of the transforming growth factor-beta (TGFB) superfamily. BMPs were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. Based on its expression early in embryogenesis, the BMP encoded by this gene has a proposed role in early development. In addition, the fact that this BMP is closely related to BMP5 and BMP7 has led to speculation of possible bone inductive activity.As of April 2009, an additional function of BMP6 has been identified as described in Nature Genetics April; 41 [4]:386-8. BMP6 is the key regulator of hepcidin, the small peptide secreted by the liver which is the major regulator of iron metabolism in mammals.

Further reading

• Celeste AJ . Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone . Proc. Natl. Acad. Sci. U.S.A. . 87 . 24 . 9843–7 . 1991 . 2263636 . 10.1073/pnas.87.24.9843 . 55270 . Iannazzi JA . Taylor RC . Hewick . RM . Rosen . V . Wang . EA . Wozney . JM . free . 1990PNAS...87.9843C .
• Schluesener HJ, Meyermann R . Immunolocalization of BMP-6, a novel TGF-beta-related cytokine, in normal and atherosclerotic smooth muscle cells . Atherosclerosis . 113 . 2 . 153–6 . 1995 . 7605353 . 10.1016/0021-9150(94)05438-O .
• Gitelman SE . Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo . J. Cell Biol. . 126 . 6 . 1595–609 . 1994 . 8089189 . 10.1083/jcb.126.6.1595 . 2290953 . Kobrin MS . Ye JQ . Lopez . AR . Lee . A . Derynck . R .
• Barnes J, Anthony CT, Wall N, Steiner MS . Bone morphogenetic protein-6 expression in normal and malignant prostate . World Journal of Urology . 13 . 6 . 337–43 . 1997 . 9116752 . 10.1007/BF00191214. 31317742 .
• Hamdy FC . Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue . Cancer Res. . 57 . 19 . 4427–31 . 1997 . 9331107 . Autzen P . Robinson MC . Horne . CH . Neal . DE . Robson . CN .
• Olavesen MG . Fine mapping of 39 ESTs on human chromosome 6p23-p25 . Genomics . 46 . 2 . 303–6 . 1998 . 9417921 . 10.1006/geno.1997.5032 . Bentley E . Mason RV . Stephens . R.J. . Ragoussis . J. .
• Rickard DJ . Bone morphogenetic protein-6 production in human osteoblastic cell lines. Selective regulation by estrogen . J. Clin. Invest. . 101 . 2 . 413–22 . 1998 . 9435314 . 10.1172/JCI119880 . 508581 . Hofbauer LC . Bonde SK . Gori . F . Spelsberg . T C . Riggs . B L .
• Tamada H . Molecular cloning and analysis of the 5'-flanking region of the human bone morphogenetic protein-6 (BMP-6) . Biochim. Biophys. Acta . 1395 . 3 . 247–51 . 1998 . 9512655 . 10.1016/S0167-4781(97)00191-7. Kitazawa R . Gohji K . Kamidono . S . Maeda . S . Kitazawa . S . 20.500.14094/D1002352. free.
• Ebisawa T . Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation . J. Cell Sci. . 112 . 20. 3519–27 . 2000 . 10504300 . Tada K . Kitajima I . Tojo . K . Sampath . TK . Kawabata . M . Miyazono . K . Imamura . T . 10.1242/jcs.112.20.3519 .
• Heikinheimo KA . Bone morphogenetic protein-6 is a marker of serous acinar cell differentiation in normal and neoplastic human salivary gland . Cancer Res. . 59 . 22 . 5815–21 . 1999 . 10582704 . Laine MA . Ritvos OV . Voutilainen . RJ . Hogan . BL . Leivo . IV .
• Ahmed N . Effect of bone morphogenetic protein-6 on haemopoietic stem cells and cytokine production in normal human bone marrow stroma . Cell Biol. Int. . 25 . 5 . 429–35 . 2001 . 11401330 . 10.1006/cbir.2000.0662 . Sammons J . Carson RJ . Khokher . MA . Hassan . HT . 85369468 .
• Shimizu M . A congenic mouse and candidate gene at the Chromosome 13 locus regulating bone density . Mamm. Genome . 13 . 7 . 335–40 . 2003 . 12140680 . 10.1007/s00335-001-2129-4 . Higuchi K . Kasai S . Tsuboyama . Tadao . Matsushita . Mutsumi . Matsumura . Takuro . Okudaira . Shuzo . Mori . Masayuki . Koizumi . Akio . 23300962 .
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . Feingold EA . Grouse LH . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free .
• Moser M . BMPER, a novel endothelial cell precursor-derived protein, antagonizes bone morphogenetic protein signaling and endothelial cell differentiation . Mol. Cell. Biol. . 23 . 16 . 5664–79 . 2003 . 12897139 . 10.1128/MCB.23.16.5664-5679.2003 . 166349 . Binder O . Wu Y . Aitsebaomo . J. . Ren . R. . Bode . C. . Bautch . V. L. . Conlon . F. L. . Patterson . C. .
• Bobacz K . Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro . Arthritis Rheum. . 48 . 9 . 2501–8 . 2003 . 13130469 . 10.1002/art.11248 . Gruber R . Soleiman A . Erlacher . L. . Smolen . J. S. . Graninger . W. B. .
• Lories RJ, Derese I, Ceuppens JL, Luyten FP . Bone morphogenetic proteins 2 and 6, expressed in arthritic synovium, are regulated by proinflammatory cytokines and differentially modulate fibroblast-like synoviocyte apoptosis . Arthritis Rheum. . 48 . 10 . 2807–18 . 2003 . 14558086 . 10.1002/art.11389 . free .
• Mungall AJ . The DNA sequence and analysis of human chromosome 6 . Nature . 425 . 6960 . 805–11 . 2003 . 14574404 . 10.1038/nature02055 . Palmer SA . Sims SK . Edwards . C. A. . Ashurst . J. L. . Wilming . L. . Jones . M. C. . Horton . R. . Hunt . S. E. . 2003Natur.425..805M . free .
• Laurikkala J . Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot . Dev. Biol. . 264 . 1 . 91–105 . 2004 . 14623234 . 10.1016/j.ydbio.2003.08.011 . Kassai Y . Pakkasjärvi L . Thesleff . Irma . Itoh . Nobuyuki . free.

Notes and References

1. Hahn GV, Cohen RB, Wozney JM, Levitz CL, Shore EM, Zasloff MA, Kaplan FS . A bone morphogenetic protein subfamily: chromosomal localization of human genes for BMP5, BMP6, and BMP7 . Genomics . 14 . 3 . 759–62 . Dec 1992 . 1427904 . 10.1016/S0888-7543(05)80181-8 . free .
2. Sauermann U, Meyermann R, Schluesener HJ . Cloning of a novel TGF-beta related cytokine, the vgr, from rat brain: cloning of and comparison to homologous human cytokines . J Neurosci Res . 33 . 1 . 142–7 . Jan 1993 . 1453478 . 10.1002/jnr.490330118 . 35064968 .
3. Web site: Entrez Gene: BMP6 bone morphogenetic protein 6.