BMP 9

Summary

Gene Symbol: BMP 9
Description: growth differentiation factor 2
Alias: BMP-9, BMP9, HHT5, growth/differentiation factor 2, bone morphogenetic protein 9
Species: human
Products:     BMP 9

Top Publications

  1. Herrera B, Dooley S, Breitkopf Heinlein K. Potential roles of bone morphogenetic protein (BMP)-9 in human liver diseases. Int J Mol Sci. 2014;15:5199-220 pubmed publisher
  2. Majumdar M, Wang E, Morris E. BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1. J Cell Physiol. 2001;189:275-84 pubmed
    ..This study shows that bone morphogenetic proteins play an important role in chondrogenesis and may prove to be potential therapeutics in cartilage repair. ..
  3. Brown M, Zhao Q, Baker K, Naik C, Chen C, Pukac L, et al. Crystal structure of BMP-9 and functional interactions with pro-region and receptors. J Biol Chem. 2005;280:25111-8 pubmed
    ..pro-region complex in cell-based assays. ..
  4. David L, Mallet C, Mazerbourg S, Feige J, Bailly S. Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood. 2007;109:1953-61 pubmed
    ..In the present study, we demonstrate that BMP9 induces the phosphorylation of Smad1/5/8 in microvascular endothelial cells, and this phosphorylation lasts over a ..
  5. Fong D, Bisson M, Laberge G, McManus S, Grenier G, Faucheux N, et al. Bone morphogenetic protein-9 activates Smad and ERK pathways and supports human osteoclast function and survival in vitro. Cell Signal. 2013;25:717-28 pubmed publisher
    ..BMP-9 signaling in human osteoclasts involves the canonical Smad-1/5/8 pathway, and the ERK pathway. ..
  6. Young K, Conley B, Romero D, Tweedie E, O Neill C, Pinz I, et al. BMP9 regulates endoglin-dependent chemokine responses in endothelial cells. Blood. 2012;120:4263-73 pubmed publisher
    b>BMP9 signaling has been implicated in hereditary hemorrhagic telangiectasia (HHT) and vascular remodeling, acting via the HHT target genes, endoglin and ALK1...
  7. Li B, Yang Y, Jiang S, Ni B, Chen K, Jiang L. Adenovirus-mediated overexpression of BMP-9 inhibits human osteosarcoma cell growth and migration through downregulation of the PI3K/AKT pathway. Int J Oncol. 2012;41:1809-19 pubmed publisher
  8. David L, Mallet C, Keramidas M, Lamandé N, Gasc J, Dupuis Girod S, et al. Bone morphogenetic protein-9 is a circulating vascular quiescence factor. Circ Res. 2008;102:914-22 pubmed publisher
    ..To identify the active factor, we tested neutralizing antibodies against BMP members and found that only the anti-BMP9 inhibited serum-induced Smad1/5 phosphorylation...
  9. Ren Y, Liu Z, Feng J, Wan H, Li J, Wang H, et al. Association of a BMP9 haplotype with ossification of the posterior longitudinal ligament (OPLL) in a Chinese population. PLoS ONE. 2012;7:e40587 pubmed publisher
    Direct or ex vivo BMP9 adenoviral gene therapy can induce massive bone formation at the injection sites and clearly promote spinal fusion...

More Information

Publications96

  1. Townson S, Martinez Hackert E, Greppi C, Lowden P, Sako D, Liu J, et al. Specificity and structure of a high affinity activin receptor-like kinase 1 (ALK1) signaling complex. J Biol Chem. 2012;287:27313-25 pubmed publisher
    ..The TGF-? family ligands BMP9 and BMP10 as well as the three type II TGF-? family receptors ActRIIA, ActRIIB, and BMPRII have been implicated in ..
  2. Park J, Shao D, Upton P, Desouza P, Adcock I, Davies R, et al. BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production. PLoS ONE. 2012;7:e30075 pubmed publisher
    ..However, increased ET-1 production by endothelial cells as a consequence of BMPR II dysfunction may be clinically relevant in the pathogenesis of PAH. ..
  3. Lopez Coviella I, Berse B, Krauss R, Thies R, Blusztajn J. Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9. Science. 2000;289:313-6 pubmed
    ..Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons. ..
  4. Wooderchak Donahue W, McDonald J, O Fallon B, Upton P, Li W, Roman B, et al. BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia. Am J Hum Genet. 2013;93:530-7 pubmed publisher
    ..Mutations in BMP9 (also known as GDF2) were identified in three unrelated probands...
  5. Herrera B, García Álvaro M, Cruz S, Walsh P, Fernandez M, Roncero C, et al. BMP9 is a proliferative and survival factor for human hepatocellular carcinoma cells. PLoS ONE. 2013;8:e69535 pubmed publisher
    ..Although originally isolated from fetal liver, little is known about BMP9, a BMP family member, and its role in liver physiology and pathology...
  6. van Meeteren L, Thorikay M, Bergqvist S, Pardali E, Stampino C, Hu Lowe D, et al. Anti-human activin receptor-like kinase 1 (ALK1) antibody attenuates bone morphogenetic protein 9 (BMP9)-induced ALK1 signaling and interferes with endothelial cell sprouting. J Biol Chem. 2012;287:18551-61 pubmed publisher
    ..The anti-hALK1 antibody interfered with bone morphogenetic protein 9 (BMP9)-induced signaling in endothelial cells...
  7. Yao Y, Jumabay M, Ly A, Radparvar M, Wang A, Abdmaulen R, et al. Crossveinless 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium. Blood. 2012;119:5037-47 pubmed publisher
    ..Thus, mutual regulation by BMP-9 and CV2 is essential in regulating the development of the vascular endothelium. ..
  8. Suzuki Y, Ohga N, Morishita Y, Hida K, Miyazono K, Watabe T. BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo. J Cell Sci. 2010;123:1684-92 pubmed publisher
    ..These findings suggest that BMP-9 signaling activates the endothelium tested in the present study via ALK-1. ..
  9. Upton P, Davies R, Trembath R, Morrell N. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells. J Biol Chem. 2009;284:15794-804 pubmed publisher
    ..b>BMP9 potently and selectively induced Smad1/5 phosphorylation and Id gene expression in HPAECs...
  10. Ye L, Kynaston H, Jiang W. Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4. Mol Cancer Res. 2008;6:1594-606 pubmed publisher
    ..BMP-9 could also prevent the migration and invasiveness of prostate cancer. This suggests that BMP-9 may function as a tumor suppressor and apoptosis regulator in prostate cancer. ..
  11. Castonguay R, Werner E, Matthews R, Presman E, Mulivor A, Solban N, et al. Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. J Biol Chem. 2011;286:30034-46 pubmed publisher
    ..human endoglin ECD-Fc bound directly, specifically, and with high affinity to bone morphogenetic proteins 9 and 10 (BMP9 and BMP10) in surface plasmon resonance (Biacore) and cell-based assays...
  12. Herrera B, Van Dinther M, Ten Dijke P, Inman G. Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation. Cancer Res. 2009;69:9254-62 pubmed publisher
    ..These studies prompted us to evaluate the potential role of BMP9 signaling in ovarian cancer...
  13. Sharff K, Song W, Luo X, Tang N, Luo J, Chen J, et al. Hey1 basic helix-loop-helix protein plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal progenitor cells. J Biol Chem. 2009;284:649-59 pubmed publisher
    ..repressor protein basic helix-loop-helix family was among the most significantly up-regulated early targets in BMP9-stimulated MSCs...
  14. Miller A, Harvey S, Thies R, Olson M. Bone morphogenetic protein-9. An autocrine/paracrine cytokine in the liver. J Biol Chem. 2000;275:17937-45 pubmed
    ..Our results depict BMP-9 as a potential autocrine/paracrine mediator in the hepatic reticuloendothelial system. ..
  15. Bidart M, Ricard N, Levet S, Samson M, Mallet C, David L, et al. BMP9 is produced by hepatocytes and circulates mainly in an active mature form complexed to its prodomain. Cell Mol Life Sci. 2012;69:313-24 pubmed publisher
    b>Bone Morphogenetic Protein 9 (BMP9) has been recently found to be the physiological ligand for the activin receptor-like kinase 1 (ALK1), and to be a major circulating vascular quiescence factor...
  16. Scharpfenecker M, Van Dinther M, Liu Z, van Bezooijen R, Zhao Q, Pukac L, et al. BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci. 2007;120:964-72 pubmed
    ..Taken together, these results suggest that BMP-9 is a physiological ALK1 ligand that plays an important role in the regulation of angiogenesis. ..
  17. Soundharrajan I, Kim D, Srisesharam S, Kuppusamy P, Sivanesan R, Choi K. Limonene promotes osteoblast differentiation and 2-deoxy-d-glucose uptake through p38MAPK and Akt signaling pathways in C2C12 skeletal muscle cells. Phytomedicine. 2018;45:41-48 pubmed publisher
  18. Liu B, Gong X, Jin Z. Effect of Danzhi decoction on expression of angiogenesis factors in patients with sequelae of pelvic inflammatory disease. Asian Pac J Trop Med. 2014;7:985-90 pubmed publisher
    ..Danzhi decoction may inhibit the expression of VEGF in the blood stasis microenvironment of SPID by targeting the cytoplasm of endometrial glandular epithelial cell. ..
  19. Ola R, Künzel S, Zhang F, Genet G, Chakraborty R, Pibouin Fragner L, et al. SMAD4 Prevents Flow Induced Arterial-Venous Malformations by Inhibiting Casein Kinase 2. Circulation. 2018;: pubmed publisher
    ..Here we addressed if SMAD4 was required for BMP9-ALK1 effects on PI3K/AKT pathway activation...
  20. Morine K, Qiao X, Paruchuri V, Aronovitz M, Mackey E, Buiten L, et al. Conditional knockout of activin like kinase-1 (ALK-1) leads to heart failure without maladaptive remodeling. Heart Vessels. 2017;32:628-636 pubmed publisher
    ..LV levels of other TGFβ-family ligands and receptors (AlK5, TBRII, BMPRII, Endoglin, BMP7, BMP9, and TGFβ1) were unchanged between groups...
  21. Pauk M, Grgurevic L, Brkljacic J, Kufner V, Bordukalo Niksic T, Grabusic K, et al. Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice. Int Orthop. 2015;39:161-72 pubmed publisher
    ..Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response...
  22. Vhora I, Lalani R, Bhatt P, Patil S, Patel H, Patel V, et al. Colloidally Stable Small Unilamellar Stearyl Amine Lipoplexes for Effective BMP-9 Gene Delivery to Stem Cells for Osteogenic Differentiation. AAPS PharmSciTech. 2018;19:3550-3560 pubmed publisher
    ..In vivo acute toxicity studies further demonstrated safety of the developed lipoplexes. Developed pegSA lipoplexes show potential for further in vivo preclinical evaluation to establish the proof of concept. ..
  23. Chen X, Zhang S, Chen X, Hu Y, Wu J, Chen S, et al. Emodin promotes the osteogenesis of MC3T3-E1 cells via BMP-9/Smad pathway and exerts a preventive effect in ovariectomized rats. Acta Biochim Biophys Sin (Shanghai). 2017;49:867-878 pubmed publisher
    ..However, emodin alone did not exert any osteoprotective effect. These results suggest that emodin may be a promising alternative agent for osteoporosis in combination therapy. ..
  24. Thangnipon W, Puangmalai N, Suwanna N, Soi ampornkul R, Phonchai R, Kotchabhakdi N, et al. Potential role of N-benzylcinnamide in inducing neuronal differentiation from human amniotic fluid mesenchymal stem cells. Neurosci Lett. 2016;610:6-12 pubmed publisher
    ..These findings suggest that N-benzylcinnamide may provide a useful adjuvant in BMP-9-induced transdifferentiation of AFMSCs into ultimately cholinergic neurons. ..
  25. Lauzon M, Drevelle O, Faucheux N. Peptides derived from the knuckle epitope of BMP-9 induce the cholinergic differentiation and inactivate GSk3beta in human SH-SY5Y neuroblastoma cells. Sci Rep. 2017;7:4695 pubmed publisher
    ..Finally, both peptides activated the PI3K/Akt pathway and inhibited GSK3beta, a current AD therapeutic target. BMP-9-derived peptides, especially SpBMP-9, with or without RA, are promising molecules that warrant further investigation. ..
  26. Ye J, Wang J, Zhu Y, Wei Q, Wang X, Yang J, et al. A thermoresponsive polydiolcitrate-gelatin scaffold and delivery system mediates effective bone formation from BMP9-transduced mesenchymal stem cells. Biomed Mater. 2016;11:025021 pubmed publisher
    ..We previously demonstrated that bone morphogenetic protein 9 (BMP9) is one of the most potent factors in inducing osteogenic differentiation of mesenchymal stem ..
  27. Beauvais S, Drevelle O, Lauzon M, Daviau A, Faucheux N. Modulation of MAPK signalling by immobilized adhesive peptides: Effect on stem cell response to BMP-9-derived peptides. Acta Biomater. 2016;31:241-251 pubmed publisher
    ..We have therefore identified a combination of bioactive polymers and BMP molecules that direct the stem cells towards bone forming cells. ..
  28. Shinohara Y, Nakamura T, Shirakata Y, Noguchi K. Bone healing capabilities of recombinant human bone morphogenetic protein-9 (rhBMP-9) with a chitosan or collagen carrier in rat calvarial defects. Dent Mater J. 2016;35:454-60 pubmed publisher
    ..It can be concluded that rhBMP-9/ACS has a potential to induce bone formation in rat calvarial defects. Further studies are required to elucidate the mechanism of bone formation induced by rhBMP-9. ..
  29. Li R, Yan Z, Ye J, Huang H, Wang Z, Wei Q, et al. The Prodomain-Containing BMP9 Produced from a Stable Line Effectively Regulates the Differentiation of Mesenchymal Stem Cells. Int J Med Sci. 2016;13:8-18 pubmed publisher
    ..Using adenovirus-mediated expression of the 14 types of BMPs we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of mesenchymal stem cells (MSCs), which was ..
  30. Li B, Tian X, Hu R, Xu F, Zhao J. Mechanism of BMP and TG2 in mesenchymal stem cell osteogenesis. Eur Rev Med Pharmacol Sci. 2015;19:4214-9 pubmed
    ..05) relatively to the control group. BMP-9 interacts with TG2 in osteogenesis of MSCs C3H10T1/2 cells. Further studies are needed to understand the exact mechanism of BMP9/PG2 interactions in osteogenesis.
  31. Kim J, Kim M, Jeong Y, Lee W, Park H, Kwon J, et al. BMP9 Induces Cord Blood-Derived Endothelial Progenitor Cell Differentiation and Ischemic Neovascularization via ALK1. Arterioscler Thromb Vasc Biol. 2015;35:2020-31 pubmed publisher
    ..The expression levels of activin receptor-like kinase 1 (ALK1) and its high-affinity ligand, bone morphogenetic protein 9 (BMP9) were markedly changed in EPC→endothelial cell differentiation...
  32. Nakamura T, Shirakata Y, Shinohara Y, Miron R, Furue K, Noguchi K. Osteogenic potential of recombinant human bone morphogenetic protein-9/absorbable collagen sponge (rhBMP-9/ACS) in rat critical size calvarial defects. Clin Oral Investig. 2017;21:1659-1665 pubmed publisher
    ..RhBMP-9 could be a potential therapeutic growth factor for future bone regenerative procedures. ..
  33. Jin H, Jeon S, Kang G, Lee H, Cho J, Lee Y. Identification of radiation response genes and proteins from mouse pulmonary tissues after high-dose per fraction irradiation of limited lung volumes. Int J Radiat Biol. 2017;93:184-193 pubmed publisher
    ..These results suggest that identified candidate genes and proteins are HDFR-specifically expressed in lung damage induced by HDFR relevant to SBRT in humans. ..
  34. Wang J, Liao J, Zhang F, Song D, Lu M, Liu J, et al. NEL-Like Molecule-1 (Nell1) Is Regulated by Bone Morphogenetic Protein 9 (BMP9) and Potentiates BMP9-Induced Osteogenic Differentiation at the Expense of Adipogenesis in Mesenchymal Stem Cells. Cell Physiol Biochem. 2017;41:484-500 pubmed publisher
    b>BMP9 induces both osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs). Nell1 is a secretory glycoprotein with osteoinductive and anti-adipogenic activities...
  35. Marei H, El Gamal A, Althani A, Afifi N, Abd Elmaksoud A, Farag A, et al. Cholinergic and dopaminergic neuronal differentiation of human adipose tissue derived mesenchymal stem cells. J Cell Physiol. 2018;233:936-945 pubmed publisher
    ..Improved protocols for MSCs induction will facilitate and ensure the reproducibility and standard production of MSCs for therapeutic applications in neurodegenerative diseases. ..
  36. Wu Y, Feng G, Song J, Zhang Y, Yu Y, Huang L, et al. TrAmplification of Human Dental Follicle Cells by piggyBac Transposon - Mediated Reversible Immortalization System. PLoS ONE. 2015;10:e0130937 pubmed publisher
    ..dDFCs) express most DFC markers and maintain multiple differentiation potential in vitro as they can be induced by BMP9 to differentiate into chondrogenic, osteogenic and adipogenic cells evidenced by gene expression and protein marker...
  37. Alaa El Din F, Patri S, Thoreau V, Rodríguez Ballesteros M, Hamade E, Bailly S, et al. Functional and splicing defect analysis of 23 ACVRL1 mutations in a cohort of patients affected by Hereditary Hemorrhagic Telangiectasia. PLoS ONE. 2015;10:e0132111 pubmed publisher
    ..The functionality of missense mutations was analyzed in response to BMP9 (specific ligand of ALK1), the maturation of the protein products and their localization were analyzed by western ..
  38. Lauzon M, Faucheux N. A small peptide derived from BMP-9 can increase the effect of bFGF and NGF on SH-SY5Y cells differentiation. Mol Cell Neurosci. 2018;88:83-92 pubmed publisher
    ..Those results strongly suggest that SpBMP-9 plus NGF or bFGF are promising therapeutic combinations against AD that required further attention. ..
  39. Franco C, Gerhardt H. Blood flow boosts BMP signaling to keep vessels in shape. J Cell Biol. 2016;214:793-5 pubmed publisher
    ..2016. J. Cell Biol http://dx.doi.org/10.1083/jcb.201603106) show that blood flow sensitizes endothelial cells to BMP9 signaling by triggering Alk1/ENG complexing to suppress cell proliferation and to recruit mural cells, thereby ..
  40. de Vinuesa A, Bocci M, Pietras K, Ten Dijke P. Targeting tumour vasculature by inhibiting activin receptor-like kinase (ALK)1 function. Biochem Soc Trans. 2016;44:1142-9 pubmed publisher
    ..Future directions in terms of new combination regimens will also be presented. ..
  41. Fang S, Liu S, Chen Y. [?-catenin is involved in BMP9-induced differentiation of C3H10T1/2 cells into cardiomyocyte-like cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016;32:750-4 pubmed
    ..role of ?-catenin in the differentiation of C3H10T1/2 cells into cardiomyocyte-like cells induced by bone morphogenetic protein 9 (BMP9)...
  42. Kienast Y, Jucknischke U, Scheiblich S, Thier M, de Wouters M, Haas A, et al. Rapid Activation of Bone Morphogenic Protein 9 by Receptor-mediated Displacement of Pro-domains. J Biol Chem. 2016;291:3395-410 pubmed publisher
    ..In the case of bone morphogenic protein 9 (BMP9), however, the pro-domains do not inhibit the bioactivity of the growth factor, and the BMP9·pro-domain ..
  43. Jiang H, Salmon R, Upton P, Wei Z, Lawera A, Davenport A, et al. The Prodomain-bound Form of Bone Morphogenetic Protein 10 Is Biologically Active on Endothelial Cells. J Biol Chem. 2016;291:2954-66 pubmed publisher
    ..Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.
  44. Li H, Zhao D, Wang S, Ding J, Zhao L. Bone morphogenetic protein?9 promotes the differentiation of mouse spleen macrophages into osteoclasts via the ALK1 receptor and ERK 1/2 pathways in vitro. Mol Med Rep. 2016;14:4545-4550 pubmed publisher
    ..The results of the present study demonstrated that BMP?9 promoted the osteoclast differentiation of osteoclast precursors via binding to the ALK1 receptor on the cell surface, and inhibiting the ERK1/2 signaling pathways in the cell. ..
  45. Niessen K, Zhang G, Ridgway J, Chen H, Yan M. ALK1 signaling regulates early postnatal lymphatic vessel development. Blood. 2010;115:1654-61 pubmed publisher
    ..Thus, our study reveals a novel aspect of ALK1 signaling in regulating lymphatic development and suggests that targeting ALK1 pathway might provide additional control of lymphangiogenesis in human diseases. ..
  46. Breitkopf Heinlein K, Meyer C, König C, Gaitantzi H, Addante A, Thomas M, et al. BMP-9 interferes with liver regeneration and promotes liver fibrosis. Gut. 2017;66:939-954 pubmed publisher
    ..Upon HSC activation, endogenous BMP-9 levels increase in vitro and in vivo and high levels of BMP-9 cause enhanced damage upon acute or chronic injury. ..
  47. Wang T, Wang P, Cao Z, Wang X, Wang D, Shen Y, et al. Effects of BMP9 and pulsed electromagnetic fields on the proliferation and osteogenic differentiation of human periodontal ligament stem cells. Bioelectromagnetics. 2017;38:63-77 pubmed publisher
    ..To detect the osteo-inductive potential of bone morphogenetic protein (BMP9), we transfected the STRO-1+ /CD146+ hPDLCSs with BMP9-expressing recombinant adenoviruses...
  48. Walker R, McCoy J, Czepnik M, Mills M, Hagg A, Walton K, et al. Molecular characterization of latent GDF8 reveals mechanisms of activation. Proc Natl Acad Sci U S A. 2018;115:E866-E875 pubmed publisher
    ..open" configuration, distinct from the latency state of TGF-? and more similar to the open state of Activin A and BMP9 (nonlatent complexes)...
  49. Kim S, Choe S, Lee D. BMP-9 enhances fibroblast growth factor 21 expression and suppresses obesity. Biochim Biophys Acta. 2016;1862:1237-46 pubmed publisher
    ..These results indicate that MB109 is also effective to treat obesity-mediated non-alcoholic fatty liver disease (NAFLD). ..
  50. Noh B, Kim Y, Park Y. A rare, low-grade appendiceal mucinous neoplasm (Pseudomyxoma peritonei) with ossification: A case report with morphoproteomic analysis of bone formation. Pathol Res Pract. 2016;212:1085-1088 pubmed publisher
    ..on the etiology of heterotopic ossification by the immunohistochemical evaluation of the novel markers such as BMP9, osteocalcin, and osteopontin. BMP9 is one of the most effective osteogenetic proteins...
  51. He F, Wang H, Ren W, Ma Y, Liao Y, Zhu J, et al. BMP9/COX-2 axial mediates high phosphate-induced calcification in vascular smooth muscle cells via Wnt/?-catenin pathway. J Cell Biochem. 2017;: pubmed publisher
    ..In the present study, we determined the relationship between high phosphate and bone morphogenetic protein 9 (BMP9) in VSMCs, the effect of BMP9 on calcification in VSMCs and the effect of COX-2 on BMP9 induced ..
  52. Osada M, Inoue O, Ding G, Shirai T, Ichise H, Hirayama K, et al. Platelet activation receptor CLEC-2 regulates blood/lymphatic vessel separation by inhibiting proliferation, migration, and tube formation of lymphatic endothelial cells. J Biol Chem. 2012;287:22241-52 pubmed publisher
    ..We propose that platelets regulate blood/lymphatic vessel separation by inhibiting the proliferation, migration, and tube formation of LECs, mainly because of the release of BMP-9 upon activation by CLEC-2/podoplanin interaction. ..
  53. Young K, Tweedie E, Conley B, Ames J, FitzSimons M, Brooks P, et al. BMP9 Crosstalk with the Hippo Pathway Regulates Endothelial Cell Matricellular and Chemokine Responses. PLoS ONE. 2015;10:e0122892 pubmed publisher
    ..expression in endothelial cells regulates subcellular localization of zyxin in focal adhesions in response to BMP9. RNA knockdown of endoglin resulted in mislocalization of zyxin and altered formation of focal adhesions...
  54. Appleby S, Mitrofan C, Crosby A, Hoenderdos K, Lodge K, Upton P, et al. Bone Morphogenetic Protein 9 Enhances Lipopolysaccharide-Induced Leukocyte Recruitment to the Vascular Endothelium. J Immunol. 2016;197:3302-3314 pubmed publisher
    ..Previous studies have suggested a role for BMP9 signaling in leukocyte recruitment to the endothelium, but the directionality of this effect and underlying ..
  55. Wan S, Liu Y, Weng Y, Wang W, Ren W, Fei C, et al. BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells. Cell Oncol (Dordr). 2014;37:363-75 pubmed publisher
    ..Here we investigated whether BMP9 (a secretary protein) may change the bone microenvironment and, by doing so, regulate the cross-talk between breast ..
  56. Wang J, Weng Y, Zhang M, Li Y, Fan M, Guo Y, et al. BMP9 inhibits the growth and migration of lung adenocarcinoma A549 cells in a bone marrow stromal cell‑derived microenvironment through the MAPK/ERK and NF-κB pathways. Oncol Rep. 2016;36:410-8 pubmed publisher
    ..b>BMP9, as the most powerful osteogenetic factor of the bone morphogenetic protein (BMP) family, can regulate the ..
  57. Li P, Li Y, Zhu L, Yang Z, He J, Wang L, et al. Targeting secreted cytokine BMP9 gates the attenuation of hepatic fibrosis. Biochim Biophys Acta Mol Basis Dis. 2018;1864:709-720 pubmed publisher
    ..Recent studies have demonstrated the functions of bone morphogenetic protein 9 (BMP9) in liver fibrosis, and thus, targeting liver-specific BMP9 abnormalities will become an ..
  58. Coskuner O, Uversky V. BMP-2 and BMP-9 binding specificities with ALK-3 in aqueous solution with dynamics. J Mol Graph Model. 2017;77:181-188 pubmed publisher
  59. Ruiz S, Chandakkar P, Zhao H, Papoin J, Chatterjee P, Christen E, et al. Tacrolimus rescues the signaling and gene expression signature of endothelial ALK1 loss-of-function and improves HHT vascular pathology. Hum Mol Genet. 2017;26:4786-4798 pubmed publisher
    ..Because HHT is caused by loss-of-function mutations in bone morphogenetic protein 9 (BMP9)-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic ..
  60. Muñoz Félix J, Cuesta C, Perretta Tejedor N, Subileau M, Lopez Hernandez F, Lopez Novoa J, et al. Identification of bone morphogenetic protein 9 (BMP9) as a novel profibrotic factor in vitro. Cell Signal. 2016;28:1252-61 pubmed publisher
    ..b>BMP9 is the main ligand for activin receptor-like kinase-1 (ALK1) TGF-?1 type I receptor and its effect on fibrosis ..
  61. Zhang J, Liang J, Huang J. Bone morphogenetic protein 9 facilitates osteocarcinoma cell apoptosis and inhibits in vivo tumor growth. Genet Mol Res. 2016;15: pubmed publisher
    ..This study investigated the role of bone morphogenetic protein 9 (BMP9), a member of the transforming growth factor (TGF)-? family, in OS development...
  62. Fujioka Kobayashi M, Schaller B, Saulacic N, Zhang Y, Miron R. Growth factor delivery of BMP9 using a novel natural bovine bone graft with integrated atelo-collagen type I: Biosynthesis, characterization, and cell behavior. J Biomed Mater Res A. 2017;105:408-418 pubmed publisher
    Within the past years, BMP9 has been characterized as one of the most osteogenic bone-inducers among the BMP family, however up until recently, BMP9 has only been available through adenovirus transfection experiments (gene therapy) not ..
  63. Zhu D, Mackenzie N, Shanahan C, Shroff R, Farquharson C, Macrae V. BMP-9 regulates the osteoblastic differentiation and calcification of vascular smooth muscle cells through an ALK1 mediated pathway. J Cell Mol Med. 2015;19:165-74 pubmed publisher
    ..These novel data demonstrate that BMP-9 induces VSMC osteogenic differentiation and calcification via ALK1, Smad and ALP dependent mechanisms. This may identify new potential therapeutic strategies for clinical intervention. ..
  64. Abdullahi W, Brzica H, Ibbotson K, Davis T, Ronaldson P. Bone morphogenetic protein-9 increases the functional expression of organic anion transporting polypeptide 1a4 at the blood-brain barrier via the activin receptor-like kinase-1 receptor. J Cereb Blood Flow Metab. 2017;37:2340-2345 pubmed publisher
    ..These data indicate that targeting ALK1 signaling with BMP-9 modulates BBB Oatp1a4 expression, presenting a unique opportunity to optimize drug delivery and improve pharmacotherapy for CNS diseases. ..
  65. Wang Y, Feng Q, Ji C, Liu X, Li L, Luo J. RUNX3 plays an important role in mediating the BMP9-induced osteogenic differentiation of mesenchymal stem cells. Int J Mol Med. 2017;40:1991-1999 pubmed publisher
    Although bone morphogenetic protein 9 (BMP9) is highly capable of promoting the osteogenic differentiation of mesenchymal stem cells (MSCs) both in vitro and in vivo, the molecular mechanisms involved remain to be fully elucidated...
  66. Acil Y, Ghoniem A, Gulses A, Kisch T, Stang F, Wiltfang J, et al. Suppression of osteoblast-related genes during osteogenic differentiation of adipose tissue derived stromal cells. J Craniomaxillofac Surg. 2017;45:33-38 pubmed publisher
    ..05). The current results indicate a restricted osteogenic differentiation potential of ASCs and suggest careful reconsideration of their use in bone tissue engineering applications. ..
  67. Lauzon M, Drevelle O, Daviau A, Faucheux N. Effects of BMP-9 and BMP-2 on the PI3K/Akt Pathway in MC3T3-E1 Preosteoblasts. Tissue Eng Part A. 2016;22:1075-85 pubmed publisher
    ..This knowledge is essential for preparing the serum-free osteogenic media required for bone tissue engineering or developing growth factor delivery systems to improve bone formation. ..
  68. Nie L, Yang X, Duan L, Huang E, Pengfei Z, Luo W, et al. The healing of alveolar bone defects with novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds. Sci Rep. 2017;7:6373 pubmed publisher
    Cells, scaffolds, and growth factors play important roles in bone regeneration. Bone morphogenetic protein 9 (BMP9), a member of BMP family, could facilitate osteogenesis by regulating growth factors and promoting angiogenesis...
  69. Ren X, Weisgerber D, Bischoff D, Lewis M, Reid R, He T, et al. Nanoparticulate Mineralized Collagen Scaffolds and BMP-9 Induce a Long-Term Bone Cartilage Construct in Human Mesenchymal Stem Cells. Adv Healthc Mater. 2016;5:1821-30 pubmed publisher
    ..Thus, the combination of BMP-9 and MC-GAG stimulates chondrocytic and osteogenic differentiation of hMSCs. ..
  70. Mitrofan C, Appleby S, Nash G, Mallat Z, Chilvers E, Upton P, et al. Bone morphogenetic protein 9 (BMP9) and BMP10 enhance tumor necrosis factor-α-induced monocyte recruitment to the vascular endothelium mainly via activin receptor-like kinase 2. J Biol Chem. 2017;292:13714-13726 pubmed publisher
    Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis...
  71. Saito T, Bokhove M, Croci R, Zamora Caballero S, Han L, Letarte M, et al. Structural Basis of the Human Endoglin-BMP9 Interaction: Insights into BMP Signaling and HHT1. Cell Rep. 2017;19:1917-1928 pubmed publisher
    ..Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9)...
  72. Verrastro Neto A, Andrade R, Correa M, Casarin R, Casati M, Pimentel S, et al. The impact of different torques for the insertion of immediately loaded implants on the peri-implant levels of angiogenesis- and bone-related markers. Int J Oral Maxillofac Surg. 2018;47:651-657 pubmed publisher
    ..Levels of vascular endothelial growth factor (VEGF), placental growth factor, bone morphogenetic protein 9 (BMP-9), periostin, osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) in the peri-..
  73. Ciumas M, Eyries M, Poirier O, Maugenre S, Dierick F, Gambaryan N, et al. Bone morphogenetic proteins protect pulmonary microvascular endothelial cells from apoptosis by upregulating ?-B-crystallin. Arterioscler Thromb Vasc Biol. 2013;33:2577-84 pubmed publisher
    ..We demonstrate a cross-talk between BMPs and CRYAB and a major effect of this regulatory interaction on resistance to apoptosis. ..
  74. Yuan H, Sehgal P. MxA Is a Novel Regulator of Endosome-Associated Transcriptional Signaling by Bone Morphogenetic Proteins 4 and 9 (BMP4 and BMP9). PLoS ONE. 2016;11:e0166382 pubmed publisher
    ..There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2...
  75. Bi J, Ge S. Potential roles of BMP9 in liver fibrosis. Int J Mol Sci. 2014;15:20656-67 pubmed publisher
    ..b>Bone morphogenetic protein 9 (BMP9) is the most recently discovered member of the BMP family...
  76. Ren W, Liu Y, Wan S, Fei C, Wang W, Chen Y, et al. BMP9 inhibits proliferation and metastasis of HER2-positive SK-BR-3 breast cancer cells through ERK1/2 and PI3K/AKT pathways. PLoS ONE. 2014;9:e96816 pubmed publisher
    b>Bone morphogenetic protein 9 (BMP9), a member of TGF-? superfamily, is reported to inhibit the growth and migration of prostate cancer, osteosarcoma and triple-negative MDA-MB-231 breast cancer cells...
  77. Khorsand B, Elangovan S, Hong L, Dewerth A, Kormann M, Salem A. A Comparative Study of the Bone Regenerative Effect of Chemically Modified RNA Encoding BMP-2 or BMP-9. AAPS J. 2017;19:438-446 pubmed publisher
    ..Together, these findings suggest that cmRNA-activated matrix encoding osteogenic molecules can provide a powerful strategy for bone regeneration with significant clinical translational potential. ..
  78. Zhang W, Zhang L, Zhou Y, Ji X, Liu J, Liu D, et al. Synergistic Effects of BMP9 and miR-548d-5p on Promoting Osteogenic Differentiation of Mesenchymal Stem Cells. Biomed Res Int. 2015;2015:309747 pubmed publisher
    ..stimulators have been reported to promote MSC osteogenic differentiation via different pathways such as bone morphogenetic protein 9 (BMP9) through influencing COX-2 and miR-548d-5p through targeting peroxisome proliferator-activated ..
  79. Lv Z, Wang C, Yuan T, Liu Y, Song T, Liu Y, et al. Bone morphogenetic protein 9 regulates tumor growth of osteosarcoma cells through the Wnt/?-catenin pathway. Oncol Rep. 2014;31:989-94 pubmed publisher
    b>Bone morphogenetic protein 9 (BMP9) is a member of the transforming growth factor-? (TGF-?) family, which has been shown to regulate the progression of several tumors...
  80. Mi L, Brown C, Gao Y, Tian Y, Le V, Walz T, et al. Structure of bone morphogenetic protein 9 procomplex. Proc Natl Acad Sci U S A. 2015;112:3710-5 pubmed publisher
    ..The observed open-armed, nonlatent conformation of pro-BMP9 and pro-BMP7 contrasts with the cross-armed, latent conformation of pro-TGF-β1...
  81. Wei Z, Salmon R, Upton P, Morrell N, Li W. Regulation of bone morphogenetic protein 9 (BMP9) by redox-dependent proteolysis. J Biol Chem. 2014;289:31150-9 pubmed publisher
    b>BMP9, a member of the TGFβ superfamily, is a homodimer that forms a signaling complex with two type I and two type II receptors...
  82. Kim M, Choi O, Pyo S, Choi S, Park C. Identification of novel ALK2 inhibitors and their effect on cancer cells. Biochem Biophys Res Commun. 2017;492:121-127 pubmed publisher
    b>Bone morphogenetic protein 9 (BMP9), a member of the TGF-? superfamily, is considered a regulator of glucose homeostasis as well as a neuronal differentiation factor...
  83. Varadaraj A, Patel P, Serrao A, Bandyopadhay T, Lee N, Jazaeri A, et al. Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia. Neoplasia. 2015;17:826-38 pubmed publisher
    ..The protein encoded by GDF2 is BMP9 and is a member of the bone morphogenetic protein family and the transforming growth factor (TGF) β superfamily ..
  84. Xu X, Li X, Yang G, Li L, Hu W, Zhang L, et al. Circulating bone morphogenetic protein-9 in relation to metabolic syndrome and insulin resistance. Sci Rep. 2017;7:17529 pubmed publisher
    ..The best cutoff values for circulating BMP-9 to predict MetS was 56.6 ng/L. Circulating BMP-9 levels were associated with the key components of MetS and IR. ..
  85. Liu X, Qin J, Luo Q, Bi Y, Zhu G, Jiang W, et al. Cross-talk between EGF and BMP9 signalling pathways regulates the osteogenic differentiation of mesenchymal stem cells. J Cell Mol Med. 2013;17:1160-72 pubmed publisher
    ..We have identified BMP9 as one of the most osteogenic BMPs in MSCs...
  86. Takahashi T, Morris E, Trippel S. Bone morphogenetic protein-2 and -9 regulate the interaction of insulin-like growth factor-I with growth plate chondrocytes. Int J Mol Med. 2007;20:53-7 pubmed
    ..Taken together, these data suggest that the BMPs may modulate the action of IGF-I via the type 1 IGF receptor and/or IGF binding proteins. ..