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https://www.readbyqxmd.com/read/27897192/pi3-kinase-inhibition-improves-vascular-malformations-in-mouse-models-of-hereditary-haemorrhagic-telangiectasia
#1
Roxana Ola, Alexandre Dubrac, Jinah Han, Feng Zhang, Jennifer S Fang, Bruno Larrivée, Monica Lee, Ana A Urarte, Jan R Kraehling, Gael Genet, Karen K Hirschi, William C Sessa, Francesc V Canals, Mariona Graupera, Minhong Yan, Lawrence H Young, Paul S Oh, Anne Eichmann
Activin receptor-like kinase 1 (ALK1) is an endothelial serine-threonine kinase receptor for bone morphogenetic proteins (BMPs) 9 and 10. Inactivating mutations in the ALK1 gene cause hereditary haemorrhagic telangiectasia type 2 (HHT2), a disabling disease characterized by excessive angiogenesis with arteriovenous malformations (AVMs). Here we show that inducible, endothelial-specific homozygous Alk1 inactivation and BMP9/10 ligand blockade both lead to AVM formation in postnatal retinal vessels and internal organs including the gastrointestinal (GI) tract in mice...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27875556/mxa-is-a-novel-regulator-of-endosome-associated-transcriptional-signaling-by-bone-morphogenetic-proteins-4-and-9-bmp4-and-bmp9
#2
Huijuan Yuan, Pravin B Sehgal
There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2...
2016: PloS One
https://www.readbyqxmd.com/read/27874028/a-mouse-model-of-hereditary-hemorrhagic-telangiectasia-generated-by-transmammary-delivered-immunoblocking-of-bmp9-and-bmp10
#3
Santiago Ruiz, Haitian Zhao, Pallavi Chandakkar, Prodyot K Chatterjee, Julien Papoin, Lionel Blanc, Christine N Metz, Fabien Campagne, Philippe Marambaud
Hereditary hemorrhagic telangiectasia (HHT) is a potentially life-threatening genetic vascular disorder caused by loss-of-function mutations in the genes encoding activin receptor-like kinase 1 (ALK1), endoglin, Smad4, and bone morphogenetic protein 9 (BMP9). Injections of mouse neonates with BMP9/10 blocking antibodies lead to HHT-like vascular defects in the postnatal retinal angiogenesis model. Mothers and their newborns share the same immunity through the transfer of maternal antibodies during lactation...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27859405/effects-of-bmp9-and-pulsed-electromagnetic-fields-on-the-proliferation-and-osteogenic-differentiation-of-human-periodontal-ligament-stem-cells
#4
Tingting Wang, Pei Wang, Zhizhong Cao, Xingxing Wang, Dalin Wang, Yaxian Shen, Da Jing, Erping Luo, Weizhong Tang
Periodontal ligament stem cells (PDLSCs) have been confirmed to have self-renewal capacity and multidifferentiation potential and are good candidates for periodontal tissue regeneration. Pulsed electromagnetic field (PEMF) has been demonstrated to promote osteogenesis in non-union fractures, partly by regulating mesenchymal stem cells or osteoblast activity. However, there is no report about the osteo-inductive effect of PEMF stimulation on human PDLSCs (hPDLSCs). Thus, we tested the hypothesis that PEMF biophysical stimulation alone has an influence on the proliferation and osteogenic differentiation of hPDLSCs...
November 11, 2016: Bioelectromagnetics
https://www.readbyqxmd.com/read/27741515/compound-genetically-engineered-mouse-models-of-cancer-reveal-dual-targeting-of-alk1-and-endoglin-as-a-synergistic-opportunity-to-impinge-on-angiogenic-tgf-%C3%AE-signaling
#5
Nikolas M Eleftheriou, Jonas Sjölund, Matteo Bocci, Eliane Cortez, Se-Jin Lee, Sara I Cunha, Kristian Pietras
Angiogenesis occurs early in tumor development, sustains primary tumor growth and provides a route for metastatic escape. The TGF-β family receptors modulate angiogenesis via endothelial-cell specific pathways. Here we investigate the interaction of two such receptors, ALK1 and endoglin, in pancreatic neuroendocrine tumors (PanNET). Independently, ALK1 and endoglin deficiencies exhibited genetically divergent phenotypes, while both highly correlate to an endothelial metagene in human and mouse PanNETs. A concurrent deficiency of both receptors synergistically decreased tumor burden to a greater extent than either individual knockdown...
October 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27725853/bone-morphogenetic-protein-9-bmp9-induces-effective-bone-formation-from-reversibly-immortalized-multipotent-adipose-derived-imad-mesenchymal-stem-cells
#6
Shun Lu, Jing Wang, Jixing Ye, Yulong Zou, Yunxiao Zhu, Qiang Wei, Xin Wang, Shengli Tang, Hao Liu, Jiaming Fan, Fugui Zhang, Evan M Farina, Maryam M Mohammed, Dongzhe Song, Junyi Liao, Jiayi Huang, Dan Guo, Minpeng Lu, Feng Liu, Jianxiang Liu, Li Li, Chao Ma, Xue Hu, Michael J Lee, Russell R Reid, Guillermo A Ameer, Dongsheng Zhou, Tongchuan He
Regenerative medicine and bone tissue engineering using mesenchymal stem cells (MSCs) hold great promise as an effective approach to bone and skeletal reconstruction. While adipose tissue harbors MSC-like progenitors, or multipotent adipose-derived cells (MADs), it is important to identify and characterize potential biological factors that can effectively induce osteogenic differentiation of MADs. To overcome the time-consuming and technically challenging process of isolating and culturing primary MADs, here we establish and characterize the reversibly immortalized mouse multipotent adipose-derived cells (iMADs)...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27712976/a-rare-low-grade-appendiceal-mucinous-neoplasm-pseudomyxoma-peritonei-with-ossification-a-case-report-with-morphoproteomic-analysis-of-bone-formation
#7
Byeong-Joo Noh, Youn Wha Kim, Yong-Koo Park
Heterotopic ossification occurring to low-grade appendiceal mucinous neoplasm (LAMN) (pseudomyxoma peritonei) is extremely rare. The pathogenetic mechanism of the tumor-related heterotopic bone formation remains as yet unconfirmed. Here, we describe a rare case of LAMN with ossification in a 72-year-old woman, and concentrate 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...
November 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27706722/bone-morphogenetic-protein-9-facilitates-osteocarcinoma-cell-apoptosis-and-inhibits-in-vivo-tumor-growth
#8
J Zhang, J H Liang, J G Huang
Osteosarcoma (OS) causes millions of death worldwide and, since there is no effective therapy, it is necessary to identify the molecular mechanism of OS, which can direct the development of new therapies. This study investigated the role of bone morphogenetic protein 9 (BMP9), a member of the transforming growth factor (TGF)-β family, in OS development. This study first examined BMP9 expression in tissue from OS patients and normal subjects. The OS cell line (MG63) and tumor cells from OS patients were then transfected with BMP9 and cell proliferation and apoptosis were assessed...
September 16, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27699987/growth-factor-delivery-of-bmp9-utilizing-a-novel-natural-bovine-bone-graft-with-integrated-atelo-collagen-type-i-biosynthesis-characterization-and-cell-behavior
#9
Masako Fujioka-Kobayashi, Benoit Schaller, Nikola Saulacic, Yufeng Zhang, Richard J Miron
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 approved for clinical use. The aim of this study was to investigate recombinant rhBMP9 versus rhBMP2 at 2 concentrations (10ng/mL and 100ng/mL) in combination with 2 bone grafts: 1)a natural bone mineral(NBM) without collagen versus 2)a novel NBM integrated with atelo-collagen type I(NBM-Col)...
October 3, 2016: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/27672213/blood-flow-boosts-bmp-signaling-to-keep-vessels-in-shape
#10
Claudio A Franco, Holger Gerhardt
Bone morphogenic proteins (BMPs) and blood flow regulate vascular remodeling and homeostasis. In this issue, Baeyens et al. (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 establishing endothelial quiescence.
September 26, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27647829/bone-morphogenetic-protein-9-enhances-lipopolysaccharide-induced-leukocyte-recruitment-to-the-vascular-endothelium
#11
Sarah L Appleby, Claudia-Gabriela Mitrofan, Alexi Crosby, Kim Hoenderdos, Katharine Lodge, Paul D Upton, Clara M Yates, Gerard B Nash, Edwin R Chilvers, Nicholas W Morrell
Bone morphogenetic protein (BMP)9 is a circulating growth factor that is part of the TGF-β superfamily and is an essential regulator of vascular endothelial homeostasis. Previous studies have suggested a role for BMP9 signaling in leukocyte recruitment to the endothelium, but the directionality of this effect and underlying mechanisms have not been elucidated. In this study, we report that BMP9 upregulates TLR4 expression in human endothelial cells and that BMP9 pretreatment synergistically increases human neutrophil recruitment to LPS-stimulated human endothelial monolayers in an in vitro flow adhesion assay...
October 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27646277/defective-fluid-shear-stress-mechanotransduction-mediates-hereditary-hemorrhagic-telangiectasia
#12
Nicolas Baeyens, Bruno Larrivée, Roxana Ola, Brielle Hayward-Piatkowskyi, Alexandre Dubrac, Billy Huang, Tyler D Ross, Brian G Coon, Elizabeth Min, Maya Tsarfati, Haibin Tong, Anne Eichmann, Martin A Schwartz
Morphogenesis of the vascular system is strongly modulated by mechanical forces from blood flow. Hereditary hemorrhagic telangiectasia (HHT) is an inherited autosomal-dominant disease in which arteriovenous malformations and telangiectasias accumulate with age. Most cases are linked to heterozygous mutations in Alk1 or Endoglin, receptors for bone morphogenetic proteins (BMPs) 9 and 10. Evidence suggests that a second hit results in clonal expansion of endothelial cells to form lesions with poor mural cell coverage that spontaneously rupture and bleed...
September 26, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27633082/effect-of-bmps-and-wnt3a-co-expression-on-the-osteogenetic-capacity-of-osteoblasts
#13
Wendong Ruan, Yuan Xue, Yaqi Zong, Chao Sun
In the present study, third‑generation autologous‑inactivated bone morphogenic protein 2 (BMP2), BMP4, BMP6, BMP7, BMP9 and Wnt3a lentiviral vectors were constructed and integrated into the genome of MC3T3‑E1 murine mesenchymal stem cells (MMSCs) to produce osteoinductive factor gene‑modified MMSCs. The transfection efficiency of each osteoinductive factor was then determined by detecting the expression levels of runt related transcription factor 2 (Runx2) mRNA. The cotransfection with combinations of two lentiviruses was performed, and the expression levels of bone γ‑carboxyglutamate protein and alkaline phosphatase in the MC3T3‑E1 cell culture supernatant were detected...
September 12, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27528761/regulation-of-the-alk1-ligands-bmp9-and-bmp10
#14
REVIEW
Wei Li, Richard M Salmon, He Jiang, Nicholas W Morrell
Bone morphogenetic protein (BMP)9 and BMP10 are high affinity ligands for activin receptor-like kinase 1 (ALK1), a type I BMP receptor mainly expressed on vascular endothelial cells (ECs). ALK1-mediated BMP9/BMP10 signalling pathways have emerged as essential in EC biology and in angiogenesis. Several genetic mutations in the genes encoding the ligands and receptors of this pathway have been reported in two cardiovascular diseases, pulmonary arterial hypertension (PAH) and hereditary haemorrhagic telangiectasia (HHT)...
August 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27517154/bmp9-alk1-inhibits-neovascularization-in-mouse-models-of-age-related-macular-degeneration
#15
Kalonji Ntumba, Naoufal Akla, S Paul Oh, Anne Eichmann, Bruno Larrivée
Age-related macular degeneration (AMD) is the leading cause of blindness in aging populations of industrialized countries. The drawbacks of inhibitors of vascular endothelial growth factor (VEGFs) currently used for the treatment of AMD, which include resistance and potential serious side-effects, require the identification of new therapeutic targets to modulate angiogenesis. BMP9 signaling through the endothelial Alk1 serine-threonine kinase receptor modulates the response of endothelial cells to VEGF and promotes vessel quiescence and maturation during development...
August 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27499862/angiogenesis-is-inhibitory-for-mammalian-digit-regeneration
#16
Ling Yu, Mingquan Yan, Jennifer Simkin, Paulina D Ketcham, Eric Leininger, Manjong Han, Ken Muneoka
The regenerating mouse digit tip is a unique model for investigating blastema formation and epimorphic regeneration in mammals. The blastema is characteristically avascular and we previously reported that blastema expression of a known anti-angiogenic factor gene, Pedf, correlated with a successful regenerative response (Yu, L., Han, M., Yan, M., Lee, E. C., Lee, J. & Muneoka, K. (2010). BMP signaling induces digit regeneration in neonatal mice. Development, 137, 551-559). Here we show that during regeneration Vegfa transcripts are not detected in the blastema but are expressed at the onset of differentiation...
June 2014: Regeneration
https://www.readbyqxmd.com/read/27466305/a-rare-colon-cancer-with-ossification-pathogenetic-analysis-of-bone-formation
#17
Byeong-Joo Noh, Youn Wha Kim, Yong-Koo Park
Heterotopic ossification occurring in colon cancer is an exceedingly rare event. The pathogenetic mechanism of tumor-related heterotopic bone formation remains unclear. Herein, we describe a rare case of colon cancer with ossification in a 76-year-old woman. We also highlight the etiology of heterotopic ossification by immunohistochemical evaluation of novel markers such as bone morphogenetic protein 9 (BMP9), osteocalcin, osteopontin, and β-catenin. BMP9 is one of the most potent osteogenetic BMPs. However, no previous research has been performed concerning BMP9 in heterotopic ossification arising in colon cancer...
July 2016: Annals of Clinical and Laboratory Science
https://www.readbyqxmd.com/read/27394662/bmp9-a-possible-alternative-drug-for-the-recently-withdrawn-bmp7-new-perspectives-for-re-implementation-by-personalized-medicine
#18
Vrinda Sreekumar, Romina Haydeé Aspera-Werz, Gauri Tendulkar, Marie Karolina Reumann, Thomas Freude, Katja Breitkopf-Heinlein, Steven Dooley, Stefan Pscherer, Björn Gunnar Ochs, Ingo Flesch, Valeska Hofmann, Andreas Klaus Nussler, Sabrina Ehnert
Promotion of rhBMP2 and rhBMP7 for the routine use to support fracture healing has been hampered by high costs, safety concerns and reasonable failure rates, imposing restrictions in its clinical use. Since there is little debate regarding its treatment potential, there is rising need for a better understanding of the mode of action of these BMPs to overcome its drawbacks and promote more efficacious treatment strategies for bone regeneration. Recently, BMP9, owing to its improved osteogenic potential, is gaining attention as a promising therapeutic alternative...
July 9, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27371840/-%C3%AE-catenin-is-involved-in-bmp9-induced-differentiation-of-c3h10t1-2-cells-into-cardiomyocyte-like-cells
#19
Songhua Fang, Shuxia Liu, Yuan Chen
Objective To investigate the role of β-catenin in the differentiation of C3H10T1/2 cells into cardiomyocyte-like cells induced by bone morphogenetic protein 9 (BMP9). Methods C3H10T1/2 cells were transfected with the recombinant adenovirus expressing BMP9 (Ad-BMP9) and differentiated into cardiomyocytes in vitro for up to 21 days. The activated level of β-catenin in the cells after cultivated with Ad-BMP9 and different concentrations of β-catenin specific inhibitor XAV-939 was detected by Western blotting...
June 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27208502/identification-of-bone-morphogenetic-protein-9-bmp9-as-a-novel-profibrotic-factor-in-vitro
#20
José M Muñoz-Félix, Cristina Cuesta, Nuria Perretta-Tejedor, Mariela Subileau, Francisco J López-Hernández, José M López-Novoa, Carlos Martínez-Salgado
Upregulated synthesis of extracellular matrix (ECM) proteins by myofibroblasts is a common phenomenon in the development of fibrosis. Although the role of TGF-β in fibrosis development has been extensively studied, the involvement of other members of this superfamily of cytokines, the bone morphogenetic proteins (BMPs) in organ fibrosis has given contradictory results. BMP9 is the main ligand for activin receptor-like kinase-1 (ALK1) TGF-β1 type I receptor and its effect on fibrosis development is unknown...
September 2016: Cellular Signalling
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