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https://www.readbyqxmd.com/read/29923343/inhibin-%C3%AE-subunit-inhibits-bmp9-induced-osteogenic-differentiation-through-blocking-bmp-smad-signal-and-activating-nf-%C3%AE%C2%BAb-signal-in-mesenchymal-stem-cells
#1
Min Huang, Ya-Lin Cheng, Ji-Tao Zeng, Xiao-Ya Su, Hong Liu
Inhibin-α, a member of the transforming growth factor (TGF-β) superfamily, has been involved in bone turnover during the menopausal transition via endocrine effects, and it was previously reported that inhibins may antagonize the function of BMPs. Certainly, one of the most important functions of BMPs is to induce osteogenic differentiation. BMP9 as one of the most potent BMPs to induce osteogenic differentiation has gotten more and more attentions. Nonetheless, the effects of inhibin-α on osteogenesis remain unknown...
June 20, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29909342/fak-and-bmp-9-synergistically-trigger-osteogenic-differentiation-and-bone-formation-of-adipose-derived-stem-cells-through-enhancing-wnt-%C3%AE-catenin-signaling
#2
Cheng Yuan, Xiaoli Gou, Jiang Deng, Zhijun Dong, Peng Ye, Zhenming Hu
BACKGROUNDS: Adipose derived stem cells (ADSCs) could undergo osteogenesis via focal adhesion kinase (FAK) and bone morphogenetic protein (BMP) 9 signals, both of which could affect Wnt-β-catenin signal, a signal pathway closely related to ADSCs osteogenesis. It's still enigma whether FAK and BMP-9 contribute to osteogenesis. Here, we examined the effect of FAK on BMP9-inducedosteogenic differentiation, unveiled the possible molecular mechanism underling this process. METHODS: In the present study, ADSCs were isolated and purified, and cells of passage 3 underwent virus mediated transfection to prepare ADSCs with stable FAK shRNA expression...
June 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29880487/bmp-bone-morphogenetic-protein-9-alk1-activin-like-kinase-receptor-type-i-signaling-prevents-hyperglycemia-induced-vascular-permeability
#3
Naoufal Akla, Claire Viallard, Natalija Popovic, Cindy Lora Gil, Przemyslaw Sapieha, Bruno Larrivée
OBJECTIVE: Diabetic macular edema is a major cause of visual impairment in diabetic retinopathy. It is caused by blood-retinal barrier breakdown that leads to vascular hyperpermeability. Current therapeutic approaches consist of retinal photocoagulation or targeting VEGF (vascular endothelial growth factor) to limit vascular leakage. However, long-term intravitreal use of anti-VEGFs is associated with potential safety issue, and the identification of alternative regulators of vascular permeability may provide safer therapeutic options...
June 7, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29843236/immunohistochemical-analysis-of-activin-receptor-like-kinase-1-acvrl1-alk1-expression-in-the-rat-and-human-hippocampus-decline-in-ca3-during-progression-of-alzheimer-s-disease
#4
Stephanie L Adams, Laurent Benayoun, Kathy Tilton, Tiffany J Mellott, Sudha Seshadri, Jan Krzysztof Blusztajn, Ivana Delalle
The pathophysiology of Alzheimer's disease (AD) includes signaling defects mediated by the transforming growth factor β-bone morphogenetic protein-growth and differentiation factor (TGFβ-BMP-GDF) family of proteins. In animal models of AD, administration of BMP9/GDF2 improves memory and reduces amyloidosis. The best characterized type I receptor of BMP9 is ALK1. We characterized ALK1 expression in the hippocampus using immunohistochemistry. In the rat, ALK1 immunoreactivity was found in CA pyramidal neurons, most frequently and robustly in the CA2 and CA3 fields...
May 18, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29789425/a-heterodimer-formed-by-bone-morphogenetic-protein-9-bmp9-and-bmp10-provides-most-bmp-biological-activity-in-plasma
#5
Emmanuelle Tillet, Marie Ouarné, Agnès Desroches-Castan, Christine Mallet, Mariela Subileau, Robin Didier, Anna Lioutsko, Guillaume Belthier, Jean-Jacques Feige, Sabine Bailly
Bone morphogenetic protein 9 (BMP9) and BMP10 are the two high-affinity ligands for the endothelial receptor activin receptor-like kinase 1 (ALK1) and are key regulators of vascular remodeling. They are both present in the blood, but their respective biological activities are still a matter of debate. The aim of the present work was to characterize their circulating forms to better understand how their activities are regulated in vivo. First, by cotransfecting BMP9 and BMP10, we found that both can form a disulfide-bonded heterodimer in vitro and that this heterodimer is functional on endothelial cells via ALK1...
May 22, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29751359/bone-morphogenetic-protein-9-as-a-key-regulator-of-liver-progenitor-cells-in-ddc-induced-cholestatic-liver-injury
#6
Annalisa Addante, Cesáreo Roncero, Laura Almalé, Nerea Lazcanoiturburu, María García-Álvaro, Margarita Fernández, Julián Sanz, Seddik Hammad, Zeribe Chike Nwosu, Se-Jin Lee, Isabel Fabregat, Steven Dooley, Peter Ten Dijke, Blanca Herrera, Aránzazu Sánchez
BACKGROUND & AIMS: Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. METHODS: WT and BMP9KO mice were submitted to DDC diet...
May 11, 2018: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/29739878/bmpr2-inhibits-activin-and-bmp-signaling-via-wild-type-alk2
#7
Oddrun Elise Olsen, Meenu Sankar, Samah Elsaadi, Hanne Hella, Glenn Buene, Sagar Ramesh Darvekar, Kristine Misund, Takenobu Katagiri, Petra Knaus, Toril Holien
TGF-β/BMP superfamily ligands require heteromeric complexes of type 1 and 2 receptors for ligand dependent downstream signaling. Activin A, a TGF-β superfamily member, inhibits growth of multiple myeloma cells, but the mechanism is unknown. We aimed to clarify how activins affect myeloma cell survival. Activin A activates the transcription factors SMAD2/3 through the ALK4 type 1 receptor, but may also activate SMAD1/5/8 through mutated variants of the type 1 receptor ALK2. We demonstrate that activin A and B activate SMAD1/5/8 in myeloma cells through endogenous wild type ALK2...
May 8, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29642505/bmp9-promotes-the-proliferation-and-migration-of-bladder-cancer-cells-through-up-regulating-lncrna-uca1
#8
Liyao Gou, Mengyao Liu, Jing Xia, Qun Wan, Yayun Jiang, Shilei Sun, Min Tang, Lan Zhou, Tongchuan He, Yan Zhang
As the most common malignant tumor of the urinary system worldwide, the bladder tumor has a high mortality rate, which is mainly due to its onset of concealment. Therefore, research into novel diagnostic markers and treatment of bladder cancer is urgently needed. BMP9 (Bone morphogenetic protein 9) is a member of BMP, which belongs to the TGF-β (transforming growth factor-β) superfamily. It has been associated with multiple tumors. We found that BMP9 is highly expressed in bladder cancer cells and it could significantly promote the proliferation and migration of bladder cancer cells...
April 8, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29542728/heart-failure-bmp9-is-an-inhibitor-of-cardiac-fibrosis
#9
Alexandra Le Bras
No abstract text is available yet for this article.
May 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29512689/microrna-155-inhibits-the-osteogenic-differentiation-of-mesenchymal-stem-cells-induced-by-bmp9-via-downregulation-of-bmp-signaling-pathway
#10
Hongxia Liu, Liang Zhong, Taixian Yuan, Sicheng Chen, Yiqing Zhou, Liqin An, Yangliu Guo, Mengtian Fan, Ya Li, Yanting Sun, Wang Li, Qiong Shi, Yaguang Weng
Previous studies have indicated that bone morphogenetic protein 9 (BMP9) can promote the osteogenic differentiation of mesenchymal stem cells (MSCs) and increase bone formation in bone diseases. However, the mechanisms involved remained poorly understood. It is necessary to investigate the specific regulatory mechanisms of osteogenic differentiation that were induced by BMP9. During the process of osteogenic differentiation induced by BMP9, the expression of microRNA-155 (miR-155) exhibited a tendency of increasing at first and then decreasing, which made us consider that miR-155 may have a modulatory role in this process, but the roles of this process have not been elucidated...
June 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29500191/primary-cilia-sensitize-endothelial-cells-to-bmp-and-prevent-excessive-vascular-regression
#11
Anne-Clémence Vion, Silvanus Alt, Alexandra Klaus-Bergmann, Anna Szymborska, Tuyu Zheng, Tijana Perovic, Adel Hammoutene, Marta Bastos Oliveira, Eireen Bartels-Klein, Irene Hollfinger, Pierre-Emmanuel Rautou, Miguel O Bernabeu, Holger Gerhardt
Blood flow shapes vascular networks by orchestrating endothelial cell behavior and function. How endothelial cells read and interpret flow-derived signals is poorly understood. Here, we show that endothelial cells in the developing mouse retina form and use luminal primary cilia to stabilize vessel connections selectively in parts of the remodeling vascular plexus experiencing low and intermediate shear stress. Inducible genetic deletion of the essential cilia component intraflagellar transport protein 88 (IFT88) in endothelial cells caused premature and random vessel regression without affecting proliferation, cell cycle progression, or apoptosis...
May 7, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29487140/bone-morphogenetic-protein-9-reduces-cardiac-fibrosis-and-improves-cardiac-function-in-heart-failure
#12
Kevin J Morine, Xiaoying Qiao, Sam York, Peter S Natov, Vikram Paruchuri, Yali Zhang, Mark J Aronovitz, Richard H Karas, Navin K Kapur
Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity...
February 27, 2018: Circulation
https://www.readbyqxmd.com/read/29478089/serum-glucocorticoid-regulated-kinase-1-as-a-novel-transcriptional-target-of-bone-morphogenetic-protein-alk1-receptor-signaling-in-vascular-endothelial-cells
#13
Mutsumi Araki, Takashi Hisamitsu, Yumi Kinugasa-Katayama, Toru Tanaka, Yukihiro Harada, Shu Nakao, Sanshiro Hanada, Shuhei Ishii, Masahide Fujita, Teruhisa Kawamura, Yoshihiko Saito, Koichi Nishiyama, Yusuke Watanabe, Osamu Nakagawa
Bone morphogenetic protein 9 (BMP9)/BMP10-ALK1 receptor signaling is essential for endothelial differentiation and vascular morphogenesis. Mutations in ALK1/ACVRL1 and other signal-related genes are implicated in human vascular diseases, and the Alk1/Acvrl1 deletion in mice causes severe impairment of vascular formation and embryonic lethality. In the microarray screen to search for novel downstream genes of ALK1 signaling, we found that the mRNA and protein expression of serum/glucocorticoid-regulated kinase 1 (SGK1) was rapidly up-regulated by the BMP9 stimulation of cultured human endothelial cells...
May 2018: Angiogenesis
https://www.readbyqxmd.com/read/29449337/alk1-loss-results-in-vascular-hyperplasia-in-mice-and-humans-through-pi3k-activation
#14
Elisenda Alsina-Sanchís, Yaiza García-Ibáñez, Ana M Figueiredo, Carla Riera-Domingo, Agnès Figueras, Xavier Matias-Guiu, Oriol Casanovas, Luisa M Botella, Miquel A Pujana, Antoni Riera-Mestre, Mariona Graupera, Francesc Viñals
OBJECTIVE: ALK1 (activin-receptor like kinase 1) is an endothelial cell-restricted receptor with high affinity for BMP (bone morphogenetic protein) 9 TGF-β (transforming growth factor-β) family member. Loss-of-function mutations in ALK1 cause a subtype of hereditary hemorrhagic telangiectasia-a rare disease characterized by vasculature malformations. Therapeutic strategies are aimed at reducing potential complications because of vascular malformations, but currently, there is no curative treatment for hereditary hemorrhagic telangiectasia...
May 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29441951/lncrna-hulc-promotes-epithelial-and-smooth-muscle-like-differentiation-of-adipose-derived-stem-cells-by-upregulation-of-bmp9
#15
Yongwei Li, Zhengfei Shan, Bin Yang, Diandong Yang, Changping Men, Yuanshan Cui, Jitao Wu
AIMS: Adipose-derived stem cells (ADSCs), a source of mesenchymal stem cells, are able to differentiate into numerous cell lineages, including epithelial and smooth muscle cells. The use of ADSCs in tissue engineering technology has become the most promising therapeutic approach for urethral reconstruction. This study aimed to explore the effect of lncRNA highly upregulated in liver cancer (HULC) on the induction of ADSCs to differentiate into epithelial and smooth-muscle-like cells. METHODS: ADSCs were isolated from a male dog, and the expression of HULC in ADSCs was overexpressed by transfection with HULC expressing vector lentivirus...
January 2, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29429074/cyclic-mechanical-stretch-enhances-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells
#16
Yang Song, Yinhong Tang, Jinlin Song, Mingxing Lei, Panpan Liang, Tiwei Fu, Xudong Su, Pengfei Zhou, Li Yang, Enyi Huang
PURPOSE: The purpose of this study was to investigate whether mechanical stretch can enhance the bone morphogenetic protein 9 (BMP9)-induced osteogenic differentiation in MSCs. METHODS: Recombinant adenoviruses were used to overexpress the BMP9 in C3H10T1/2 MSCs. Cells were seeded onto six-well BioFlex collagen I-coated plates and subjected to cyclic mechanical stretch [6% elongation at 60 cycles/minute (1 Hz)] in a Flexercell FX-4000 strain unit for up to 12 hours...
April 2018: International Orthopaedics
https://www.readbyqxmd.com/read/29377252/hmox1-promotes-osteogenic-differentiation-at-the-expense-of-reduced-adipogenic-differentiation-induced-by-bmp9-in-c3h10t1-2-cells
#17
Xiaohua Liu, Caixia Ji, Li Xu, TingTing Yu, Chaoqun Dong, Jinyong Luo
Mesenchymal stem cells (MSCs) are multipotent progenitors that can differentiate into a variety of cell types under proper stimuli. Bone morphogenetic protein 9 (BMP9) is able to simultaneously induce both adipogenic and osteogenic differentiation of MSCs although the regulatory molecules involved remain to be fully identified and characterized. Heme oxygenase 1 (Hmox1) plays an essential role not only in fat metabolism, but also in bone development. In the present study, we investigated the functional role of Hmox1 in BMP9-induced osteogenic/adipogenic differentiation in MSCs line C3H10T1/2 and probed the possible mechanism involved...
January 29, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29348202/molecular-characterization-of-latent-gdf8-reveals-mechanisms-of-activation
#18
Ryan G Walker, Jason C McCoy, Magdalena Czepnik, Melanie J Mills, Adam Hagg, Kelly L Walton, Thomas R Cotton, Marko Hyvönen, Richard T Lee, Paul Gregorevic, Craig A Harrison, Thomas B Thompson
Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or "triggered" state where the prodomain remains in complex with the mature domain...
January 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29340096/crispr-cas9-mediated-reversibly-immortalized-mouse-bone-marrow-stromal-stem-cells-bmscs-retain-multipotent-features-of-mesenchymal-stem-cells-mscs
#19
Xue Hu, Li Li, Xinyi Yu, Ruyi Zhang, Shujuan Yan, Zongyue Zeng, Yi Shu, Chen Zhao, Xingye Wu, Jiayan Lei, Yasha Li, Wenwen Zhang, Chao Yang, Ke Wu, Ying Wu, Liping An, Shifeng Huang, Xiaojuan Ji, Cheng Gong, Chengfu Yuan, Linghuan Zhang, Wei Liu, Bo Huang, Yixiao Feng, Bo Zhang, Rex C Haydon, Hue H Luu, Russell R Reid, Michael J Lee, Jennifer Moriatis Wolf, Zebo Yu, Tong-Chuan He
Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells that can undergo self-renewal and differentiate into multi-lineages. Bone marrow stromal stem cells (BMSCs) represent one of the most commonly-used MSCs. In order to overcome the technical challenge of maintaining primary BMSCs in long-term culture, here we seek to establish reversibly immortalized mouse BMSCs (imBMSCs). By exploiting CRISPR/Cas9-based homology-directed-repair (HDR) mechanism, we target SV40T to mouse Rosa26 locus and efficiently immortalize mouse BMSCs (i...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312637/notch-signaling-negatively-regulates-bmp9-induced-osteogenic-differentiation-of-mesenchymal-progenitor-cells-by-inhibiting-junb-expression
#20
Nan Wang, Wei Liu, Tao Tan, Chao-Qun Dong, Duan-Yang Lin, Jun Zhao, Chang Yu, Xiao-Ji Luo
Although interaction between BMP and Notch signaling has been demonstrated to be crucial for osteogenic differentiation of mesenchymal stem cells (MSCs), the precise molecular mechanism remains unknown. Here, we show that Notch intracellular domain (NICD) overexpression inhibits BMP9-induced C3H10T1/2 cell osteogenesis in vivo and in vitro . Our results show that activated Notch signaling results in down-regulation of Runx2 and early osteogenesis differentiation factors, without affecting p-Smad1/5/8 expression, and that blocking Notch signaling with DAPT (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester) significantly increases p-Smad1/5/8 expression...
December 12, 2017: Oncotarget
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