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https://www.readbyqxmd.com/read/28197731/comparison-of-the-effects-of-recombinant-human-bone-morphogenetic-protein-2-and-9-on-bone-formation-in-rat-calvarial-critical-size-defects
#1
Toshiaki Nakamura, Yoshinori Shirakata, Yukiya Shinohara, Richard J Miron, Kozue Hasegawa-Nakamura, Masako Fujioka-Kobayashi, Kazuyuki Noguchi
OBJECTIVES: Among bone morphogenetic protein (BMP) family members, BMP-2 and BMP-9 have demonstrated potent osteoinductive potential. However, in vivo differences in their potential for bone regeneration remain unclear. The present study aimed to compare the effects of recombinant human (rh) BMP-2 and rhBMP-9 on bone formation in rat calvarial critical-size defects (CSD). MATERIALS AND METHODS: Twenty-eight Wistar rats surgically received two calvarial defects bilaterally in each parietal bone...
February 14, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/28191670/involvement-of-the-phosphoinositide-3-kinase-akt-signaling-pathway-in-bone-morphogenetic-protein-9-stimulated-osteogenic-differentiation-and-stromal-cell-derived-factor-1-production-in-human-periodontal-ligament-fibroblasts
#2
Kirara Furue, Kotaro Sena, Kenji Sakoda, Toshiaki Nakamura, Kazuyuki Noguchi
Recent studies have shown that bone morphogenetic protein 9 (BMP-9) can induce osteogenic differentiation in human periodontal stem cells and human periodontal ligament fibroblasts (PDLFs). Bone morphogenetic protein 9 may be used in periodontal tissue regeneration because of its potent osteoinductive ability. Human periodontal ligament cells also have been demonstrated to produce stromal cell-derived factor 1 (SDF-1), which is important for stem-cell homing and recruitment to injured sites. In the present study, we examined the involvement of the phosphoinositide 3-kinase (PI3K)/Akt signaling axis in osteogenic differentiation and SDF-1 production in human PDLFs stimulated with BMP-9 in osteogenic medium supplemented with dexamethasone and ascorbic acid...
February 13, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/28133920/dual-targeting-of-vascular-endothelial-growth-factor-and-bone-morphogenetic-protein-9-10-impairs-tumor-growth-through-inhibition-of-angiogenesis
#3
Yuichi Akatsu, Yasuhiro Yoshimatsu, Taishi Tomizawa, Kazuki Takahashi, Akihiro Katsura, Kohei Miyazono, Tetsuro Watabe
Clinical development of anti-angiogenic agents has been a major landmark in cancer therapy for several types of cancers. Signals mediated by both vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP)-9 and 10 have been implicated in tumor angiogenesis. However, previous studies have shown that targeting the individual signals was not sufficiently effective in retarding tumor growth in certain preclinical and clinical conditions. In the present study, we developed a novel decoy chimeric receptor that traps both VEGF and BMP-9/10...
January 2017: Cancer Science
https://www.readbyqxmd.com/read/28074350/a-comparative-study-of-the-bone-regenerative-effect-of-chemically-modified-rna-encoding-bmp-2-or-bmp-9
#4
Behnoush Khorsand, Satheesh Elangovan, Liu Hong, Alexander Dewerth, Michael S D Kormann, Aliasger K Salem
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2...
January 10, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28054585/osseous-differentiation-of-human-fat-tissue-grafts-from-tissue-engineering-to-tissue-differentiation
#5
Maryna Bondarava, Chiara Cattaneo, Bin Ren, Wolfgang E Thasler, Volkmar Jansson, Peter E Müller, Oliver B Betz
Conventional bone tissue engineering approaches require isolation and in vitro propagation of autologous cells, followed by seeding on a variety of scaffolds. Those protracted procedures impede the clinical applications. Here we report the transdifferentiation of human fat tissue fragments retrieved from subcutaneous fat into tissue with bone characteristics in vitro without prior cell isolation and propagation. 3D collagen-I cultures of human fat tissue were cultivated either in growth medium or in osteogenic medium (OM) with or without addition of Bone Morphogenetic Proteins (BMPs) BMP-2, BMP-7 or BMP-9...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28031424/the-dart-study-results-from-the-dose-escalation-and-expansion-cohorts-evaluating-the-combination-of-dalantercept-plus-axitinib-in-advanced-renal-cell-carcinoma
#6
Martin H Voss, Rupal S Bhatt, Elizabeth R Plimack, Brian I Rini, Robert S Alter, J Thaddeus Beck, Dawn Wilson, Xiaosha Zhang, Musa Mutyaba, Chad Glasser, Kenneth M Attie, Matthew L Sherman, Shuchi S Pandya, Michael Atkins
PURPOSE: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and vascular endothelial growth factor (VEGF) signaling results in augmented inhibition of tumor growth in renal cell carcinoma (RCC) xenograft models. Dalantercept is an ALK1 receptor-fusion protein that acts as a ligand trap for bone morphogenetic proteins (BMP) 9 and 10. The DART Study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of dalantercept plus axitinib in patients with advanced RCC and determined the optimal dose for further testing...
December 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27940998/decreased-circulating-bmp-9-levels-in-patients-with-type%C3%A2-2-diabetes-is-a-signature-of-insulin-resistance
#7
Yong Luo, Ling Li, Xiaohui Xu, Tong Wu, Mengliu Yang, Cheng Zhang, Huaming Mou, Tingting Zhou, Yanjun Jia, Chenrongrong Cai, Hua Liu, Gangyi Yang, Xianxiang Zhang
Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic-hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27842921/suppression-of-osteoblast-related-genes-during-osteogenic-differentiation-of-adipose-tissue-derived-stromal-cells
#8
Yahya Açil, Amir Alexander Ghoniem, Aydin Gülses, Tobias Kisch, Felix Stang, Jörg Wiltfang, Matthias Gierloff
Recent studies indicated a lower osteogenic differentiation potential of adipose tissue-derived stromal cells (ASCs) compared to bone marrow derived mesenchymal stromal cells. The aim of this study was to evaluate the effects of potent combinations of highly osteogenic bone morphogenetic proteins (BMPs) in order to enhance the osteogenic differentiation potential of ASCs. Human ASCs were cultured for 10 days in the presence of osteogenic medium consisting of dexamethasone, ß-glycerophosphate and ascorbat-2-phosphate (OM) supplemented with BMP-2, BMP-6, BMP-9+IGF-2 and BMP-2,-6,-9 (day 1+2: 50 ng/ml, days 3-6: 100 ng/ml, days 7-10: 200 ng/ml)...
January 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/27826623/-corrigendum-adenovirus-mediated-overexpression-of-bmp-9-inhibits-human-osteosarcoma-cell-growth-and-migration-through-downregulation-of-the-pi3k-akt-pathway
#9
Bo Li, Yuehua Yang, Shengdan Jiang, Binbin Ni, Ke Chen, Leisheng Jiang
Following the publication of this article, an interested reader drew to our attention an anomaly associated with the presentation of the western blots in Fig. 4B and C. These contained the same GAPDH control data, even though Fig. 4B and C were intended to show the inhibition of osteosarcoma cell migration by a recombinant adenovirus (ad) expressing bone morphogenetic protein 9 (adBMP-9) in two different cell lines, MG-63 and HOS, respectively. After having re-examined our original data, we realize that the same GAPDH control bands were inadvertently selected for Fig...
November 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27748860/bone-morphogenetic-protein%C3%A2-9-promotes-the-differentiation-of-mouse-spleen-macrophages-into-osteoclasts-via-the-alk1-receptor-and-erk-1-2-pathways-in%C3%A2-vitro
#10
Hai Li, Dahang Zhao, Shengjing Wang, Jing Ding, Li Zhao
It has been confirmed that bone morphogenetic protein-9 (BMP-9) promotes the differentiation of osteoblasts. However, the ways in which BMP‑9 exerts its effects on the differentiation of osteoclasts and bone resorption remain to be elucidated. The present study was designed to investigate the roles and the molecular mechanism of BMP‑9 on the proliferation and differentiation of osteoclast precursors in vitro. Mouse spleen macrophages (RAW 264.7 cells) were cultured in the presence of receptor activator for nuclear factor‑κb ligand (RANKL) in vitro...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27726024/osteogenic-potential-of-recombinant-human-bone-morphogenetic-protein-9-absorbable-collagen-sponge-rhbmp-9-acs-in-rat-critical-size-calvarial-defects
#11
Toshiaki Nakamura, Yoshinori Shirakata, Yukiya Shinohara, Richard J Miron, Kirara Furue, Kazuyuki Noguchi
OBJECTIVES: It has been reported that bone morphogenetic protein (BMP)-9 has potent osteoinductive properties among the BMP family by adenovirus-transfection experiments. We very recently reported that absorbable collagen sponge (ACS) as a carrier for recombinant human (rh) BMP-9, compared with chitosan sponge, was suitable for inducing bone healing/regeneration by BMP-9 in a rat calvarial defect model. The aim of this study was to evaluate different doses of rhBMP-9/ACS on new bone formation in rat critical size calvarial defects...
October 11, 2016: Clinical Oral Investigations
https://www.readbyqxmd.com/read/27650540/bone-morphogenetic-protein-9-is-a-potent-growth-inhibitor-of-hepatocellular-carcinoma-and-reduces-the-liver-cancer-stem-cells-population
#12
Jae Woo Jung, So-Mi Yoon, Subin Kim, Yun-Hui Jeon, Byung-Hak Yoon, Su-Geun Yang, Min Kyoung Kim, Senyon Choe, Mario Meng-Chiang Kuo
The biological role of BMP-9 signaling in liver cancer remains dubious. To explore the potential use of BMP-9 signaling for anti-cancer therapy, we used recombinant human BMP-9, which we referred to as MB109, to study the effect on growth of fifteen hepatocellular carcinoma (HCC) cell lines. MB109 effectively inhibits the proliferation of nine HCC cells in vitro. The anti-proliferative effect was found to be induced by turning on p21 signaling, which caused survivin suppression and G0/G1 cell cycle arrest. ID3 was identified to be the mediator of the MB109-induced p21 expression...
September 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27647829/bone-morphogenetic-protein-9-enhances-lipopolysaccharide-induced-leukocyte-recruitment-to-the-vascular-endothelium
#13
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/27528762/targeting-tumour-vasculature-by-inhibiting-activin-receptor-like-kinase-alk-1-function
#14
REVIEW
Amaya García de Vinuesa, Matteo Bocci, Kristian Pietras, Peter Ten Dijke
Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs)...
August 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27528761/regulation-of-the-alk1-ligands-bmp9-and-bmp10
#15
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/27477105/effects-of-bmp-9-and-bmp-2-on-the-pi3k-akt-pathway-in-mc3t3-e1-preosteoblasts
#16
Marc-Antoine Lauzon, Olivier Drevelle, Alex Daviau, Nathalie Faucheux
The bone morphogenetic proteins (BMPs), which are involved in bone formation and repair, play an important role in tissue engineering. For example, BMP-9 and BMP-2, which are members of different BMP subfamilies, are osteoinductive factors. However, several studies have recently shown that BMP-9 is more osteogenic than BMP-2. We have previously shown that fetal bovine serum (FBS) strongly enhances the osteoblast differentiation of murine preosteoblasts (MC3T3-E1) to BMP-9 but not to BMP-2. This effect is mimicked by IGF-2, which primarily activates the PI3K/Akt pathway, but how Akt phosphorylation sites are implicated in such differentiation is unclear...
September 2016: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/27373274/structure-and-activation-of-pro-activin-a
#17
Xuelu Wang, Gerhard Fischer, Marko Hyvönen
Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain...
2016: Nature Communications
https://www.readbyqxmd.com/read/27284602/-recombinant-adenovirus-mediated-bone-morphogenetic-protein-9-and-erythropoietin-genes-co-transfection-in-promoting-osteogenic-differentiation-of-adipose-derived-stem-cells-in-vitro
#18
Guangde Zhang, Chengshuai Su, Xia Jin, Shimao Yang, Dianji Fang, Yanwei Guo
OBJECTIVE: To investigate the effect of recombinant adenovirus-mediated bone morphogenetic protein 9 (BMP-9) and erythropoietin (EPO) genes co-transfection on osteogenic differentiation of adipose-derived stem cells (ADSCs) in vitro. METHODS: The inguinal adipose tissue was harvested from 4-month-old New Zealand rabbits, ADSCs were isolated with enzyme digestion and adherence method, and multipotent differentiation capacity was identified. The 3rd generation ADSCs were divided into 5 groups: normal cells (group A), empty plasmid control group (group B), BMP-9 or EPO recombinant adenovirus transfected cells (groups C and D), BMP-9 and EPO recombinant adenovirus co-transfected cells (group E)...
March 2016: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/27281870/-effect-of-hey1-expression-on-osteogenic-differentiation-and-proliferation-of-c3h10t1-2-cells-induced-by-bone-morphogenetic-protein-9
#19
Miao Wang, Nan Wang, Zhengxue Quan, Xiaoji Luo
OBJECTIVE: To investigate the effect of Notch signaling pathway important target Hey1 expression on the differentiation and proliferation of C3H10T1/2 cells induced by bone morphogenetic protein 9 (BMP-9). METHODS: Hey1 lentivirus and Hey1 short hairpin RNA lentivirus were constructed and used to infect C3H10T1/2 cells to change the expression level of Hey1 in C3H10T1/2 cells. C3H10T1/2 cells infected with LV-Blank (empty plasmid) as control. The Hey1 expression levels of different groups were detected by fluorescence microscope, real-time fluorescence quantitative PCR, and Western blot...
March 2016: Chinese Journal of Reparative and Reconstructive Surgery
https://www.readbyqxmd.com/read/27275929/nanoparticulate-mineralized-collagen-scaffolds-and-bmp-9-induce-a-long-term-bone-cartilage-construct-in-human-mesenchymal-stem-cells
#20
Xiaoyan Ren, Daniel W Weisgerber, David Bischoff, Michael S Lewis, Russell R Reid, Tong-Chuan He, Dean T Yamaguchi, Timothy A Miller, Brendan A C Harley, Justine C Lee
Engineering the osteochondral junction requires fabrication of a microenvironment that supports both osteogenesis and chondrogenesis. Multiphasic scaffold strategies utilizing a combination of soluble factors and extracellular matrix components are ideally suited for such applications. In this work, the contribution of an osteogenic nanoparticulate mineralized glycosaminoglycan scaffold (MC-GAG) and a dually chondrogenic and osteogenic growth factor, BMP-9, in the differentiation of primary human mesenchymal stem cells (hMSCs) is evaluated...
July 2016: Advanced Healthcare Materials
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