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BMP-9

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https://www.readbyqxmd.com/read/28387157/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
#1
Wazir Abdullahi, Hrvoje Brzica, Kathryn Ibbotson, Thomas P Davis, Patrick T Ronaldson
Targeting uptake transporters such as organic anion transporting polypeptide 1a4 (Oatp1a4) at the blood-brain barrier (BBB) can facilitate central nervous system (CNS) drug delivery. Effective blood-to-brain drug transport via this strategy requires characterization of mechanisms that modulate BBB transporter expression and/or activity. Here, we show that activation of activin receptor-like kinase (ALK)-1 using bone morphogenetic protein (BMP)-9 increases Oatp1a4 protein expression in rat brain microvessels in vivo...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28369825/cholinergic-and-dopaminergic-neuronal-differentiation-of-human-adipose-tissue-derived-mesenchymal-stem-cells
#2
H E Marei, A El-Gamal, A Althani, N Afifi, A Abd-Elmaksoud, A Farag, C Cenciarelli, Thomas Caceci, Anwarul Hasan
Mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into various cell types such as cartilage, bone, and fat cells. Recent studies have shown that induction of MSCs in vitro by growth factors including epidermal growth factor (EGF) and fibroblast growth factor (FGF2) causes them to differentiate into neural like cells. These cultures also express ChAT, a cholinergic marker; and TH, a dopaminergic marker for neural cells. To establish a protocol with maximum differentiation potential, we examined MSCs under three experimental culture conditions using neural induction media containing FGF2, EGF, BMP-9, retinoic acid and heparin...
March 30, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28336518/bmp-9-interferes-with-liver-regeneration-and-promotes-liver-fibrosis
#3
Katja Breitkopf-Heinlein, Christoph Meyer, Courtney König, Haristi Gaitantzi, Annalisa Addante, Maria Thomas, Eliza Wiercinska, Chen Cai, Qi Li, Fengqi Wan, Claus Hellerbrand, Nektarios A Valous, Maximilian Hahnel, Christian Ehlting, Johannes G Bode, Stephanie Müller-Bohl, Ursula Klingmüller, Jutta Altenöder, Iryna Ilkavets, Marie-José Goumans, Lukas J A C Hawinkels, Se-Jin Lee, Matthias Wieland, Carolin Mogler, Matthias P Ebert, Blanca Herrera, Hellmut Augustin, Aránzazu Sánchez, Steven Dooley, Peter Ten Dijke
OBJECTIVE: Bone morphogenetic protein (BMP)-9, a member of the transforming growth factor-β family of cytokines, is constitutively produced in the liver. Systemic levels act on many organs and tissues including bone and endothelium, but little is known about its hepatic functions in health and disease. DESIGN: Levels of BMP-9 and its receptors were analysed in primary liver cells. Direct effects of BMP-9 on hepatic stellate cells (HSCs) and hepatocytes were studied in vitro, and the role of BMP-9 was examined in acute and chronic liver injury models in mice...
May 2017: Gut
https://www.readbyqxmd.com/read/28249039/repair-of-critical-sized-cranial-defects-with-bmp9-transduced-calvarial-cells-delivered-in-a-thermoresponsive-scaffold
#4
Zari P Dumanian, Viktor Tollemar, Jixing Ye, Minpeng Lu, Yunxiao Zhu, Junyi Liao, Guillermo A Ameer, Tong-Chuan He, Russell R Reid
Large skeletal defects caused by trauma, congenital malformations, and post-oncologic resections of the calvarium present major challenges to the reconstructive surgeon. We previously identified BMP-9 as the most osteogenic BMP in vitro and in vivo. Here we sought to investigate the bone regenerative capacity of murine-derived calvarial mesenchymal progenitor cells (iCALs) transduced by BMP-9 in the context of healing critical-sized calvarial defects. To accomplish this, the transduced cells were delivered to the defect site within a thermoresponsive biodegradable scaffold consisting of poly(polyethylene glycol citrate-co-N-isopropylacrylamide mixed with gelatin (PPCN-g)...
2017: PloS One
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
#5
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
#6
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
#7
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
#8
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...
March 2017: AAPS Journal
https://www.readbyqxmd.com/read/28054585/osseous-differentiation-of-human-fat-tissue-grafts-from-tissue-engineering-to-tissue-differentiation
#9
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
#10
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 B Atkins
Purpose: Activin receptor-like kinase 1 (ALK1) is a novel target in angiogenesis. Concurrent targeting of ALK1 and 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 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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...
November 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27647829/bone-morphogenetic-protein-9-enhances-lipopolysaccharide-induced-leukocyte-recruitment-to-the-vascular-endothelium
#17
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
#18
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
#19
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
#20
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
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