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https://www.readbyqxmd.com/read/28973643/tacrolimus-rescues-the-signaling-and-gene-expression-signature-of-endothelial-alk1-loss-of-function-and-improves-hht-vascular-pathology
#1
Santiago Ruiz, Pallavi Chandakkar, Haitian Zhao, Julien Papoin, Prodyot K Chatterjee, Erica Christen, Christine N Metz, Lionel Blanc, Fabien Campagne, Philippe Marambaud
Hereditary hemorrhagic telangiectasia (HHT) is a highly debilitating and life-threatening genetic vascular disorder arising from endothelial cell (EC) proliferation and hypervascularization, for which no cure exists. Because HHT is caused by loss-of-function mutations in BMP9-ALK1-Smad1/5/8 signaling, interventions aimed at activating this pathway are of therapeutic value. We interrogated the whole-transcriptome in human umbilical vein ECs (HUVECs) and found that ALK1 signaling inhibition was associated with a specific pro-angiogenic gene expression signature, which included a significant elevation of DLL4 expression...
September 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28956179/mir-149-promotes-human-osteocarcinoma-progression-via-targeting-bone-morphogenetic-protein-9-bmp9
#2
Zikang Xie, Jianda Xu, Libo Peng, Yi Gao, Hong Zhao, Yuxing Qu
OBJECTIVES: To investigate the roles of miR-149 in the progression of human osteosarcoma (OS). RESULTS: miR-149 level was upregulated in tissues from OS patients more than in normal subjects. Cell proliferation and apoptosis assays revealed that miR-149 increased cell proliferation and inhibited cell apoptosis in OS cell line (MG63). An increase of Bcl-2 gene expression and a decrease of cleaved-caspase-3, and cleaved-PARP expression were observed in MG63 cells with transfection of miR-149...
September 27, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28955765/identification-of-ligand-selective-peptidic-actriib-antagonists-using-phage-display-technology
#3
Kotaro Sakamoto, Yoko Kanematsu-Yamaki, Yusuke Kamada, Masahiro Oka, Toshiyuki Ohnishi, Masanori Miwa, Taiji Asami, Hiroshi Inooka
ActRIIB (activin receptor type-2B) is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN), growth differentiation factor 11 (GDF11), and bone morphogenetic protein 9 (BMP9). Notably, the protein-protein interaction (PPI) between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia...
September 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28949445/impact-of-selective-anti-bmp9-treatment-on-tumor-cells-and-tumor-angiogenesis
#4
(no author information available yet)
The role of bone morphogenic protein 9 (BMP9) signaling in angiogenesis has been controversial, with a number of studies showing that it acts either as a pro-angiogenic or, conversely, as an anti-angiogenic factor in a context-dependent manner. Notably, BMP9 was also reported to function in both pro- or anti-tumorigenic roles during tumor progression. It has therefore remained unclear, whether selective BMP9 inhibition is a useful target for antibody therapy of cancer. To shed light on these questions, we characterized BMP9 expression in plasma of patients with different cancer indications and found elevated levels of pro-domains and precursor BMP9 with a strong response in renal cell carcinoma (RCC)...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28881833/lncrna-h19-mediates-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells-mscs-through-notch-signaling
#5
Junyi Liao, Xinyi Yu, Xue Hu, Jiaming Fan, Jing Wang, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Yi Shu, Ruyi Zhang, Shujuan Yan, Yasha Li, Wenwen Zhang, Jing Cui, Chao Ma, Li Li, Yichun Yu, Tingting Wu, Xingye Wu, Jiayan Lei, Jia Wang, Chao Yang, Ke Wu, Ying Wu, Jun Tang, Bai-Cheng He, Zhong-Liang Deng, Hue H Luu, Rex C Haydon, Russell R Reid, Michael J Lee, Jennifer Moriatis Wolf, Wei Huang, Tong-Chuan He
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can undergo self-renewal and differentiate into multiple lineages. Osteogenic differentiation from MSCs is a well-orchestrated process and regulated by multiple signaling pathways. We previously demonstrated that BMP9 is one of the most potent osteogenic factors. However, molecular mechanism through which BMP9 governs osteoblastic differentiation remains to be fully understood. Increasing evidence indicates noncoding RNAs (ncRNAs) may play important regulatory roles in many physiological and/or pathologic processes...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28782519/identification-of-novel-alk2-inhibitors-and-their-effect-on-cancer-cells
#6
Minsung Kim, Okran Choi, Suhkneung Pyo, Sang Un Choi, Chi Hoon Park
Bone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, is considered a regulator of glucose homeostasis as well as a neuronal differentiation factor. BMP9 induces phosphorylation of Smad1/5 through activin receptor-like kinase 1 and 2 (ALK1 and ALK2). Recently, many studies have shown that BMP9 contributes to tumorigenesis, and aberrant ALK2 expression is involved in many diseases. To investigate the role of BMP9-ALK2 signaling in cancer cells, we used TF-1 cells that require granulocyte-macrophage colony-stimulating factor (GM-CSF) for cell proliferation...
October 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28751863/bone-morphogenetic-protein-9-protects-against-neonatal-hyperoxia-induced-impairment-of-alveolarization-and-pulmonary-inflammation
#7
Xueyu Chen, Mar Orriols, Frans J Walther, El Houari Laghmani, Annemarie M Hoogeboom, Anne C B Hogen-Esch, Pieter S Hiemstra, Gert Folkerts, Marie-José T H Goumans, Peter Ten Dijke, Nicholas W Morrell, Gerry T M Wagenaar
Aim: Effective treatment of premature infants with bronchopulmonary dysplasia (BPD) is lacking. We hypothesize that bone morphogenetic protein 9 (BMP9), a ligand of the TGF-β family that binds to the activin receptor-like kinase 1 (ALK1)-BMP receptor type 2 (BMPR2) receptor complex, may be a novel therapeutic option for BPD. Therefore, we investigated the cardiopulmonary effects of BMP9 in neonatal Wistar rats with hyperoxia-induced BPD. Methods: Directly after birth Wistar rat pups were exposed to 100% oxygen for 10 days...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28743897/the-healing-of-alveolar-bone-defects-with-novel-bio-implants-composed-of-ad-bmp9-transfected-rdfcs-and-cha-scaffolds
#8
Li Nie, Xia Yang, Liang Duan, Enyi Huang, Zhou Pengfei, Wenping Luo, Yan Zhang, Xingqi Zeng, Ye Qiu, Ting Cai, Conghua Li
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. Similar to other stem cells, rat dental follicle stem cells (rDFCs), the precursor cells of cementoblasts, osteoblasts and periodontal ligament cells, can self-renew and exhibit multipotential capacity. Coralline hydroxyapatite (CHA) has good biocompatibility and conductivity required for bone tissue engineering...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28668938/lncrna-h19-mediates-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells-mscs-through-notch-signaling
#9
Junyi Liao, Xinyi Yu, Xue Hu, Jiaming Fan, Jing Wang, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Yi Shu, Ruyi Zhang, Shujuan Yan, Yasha Li, Wenwen Zhang, Jing Cui, Chao Ma, Li Li, Yichun Yu, Tingting Wu, Xingye Wu, Jiayan Lei, Jia Wang, Chao Yang, Ke Wu, Ying Wu, Jun Tang, Bai-Cheng He, Zhong-Liang Deng, Hue H Luu, Rex C Haydon, Russell R Reid, Michael J Lee, Jennifer Moriatis Wolf, Wei Huang, Tong-Chuan He
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can undergo self-renewal and differentiate into multiple lineages. Osteogenic differentiation from MSCs is a well-orchestrated process and regulated by multiple signaling pathways. We previously demonstrated that BMP9 is one of the most potent osteogenic factors. However, molecular mechanism through which BMP9 governs osteoblastic differentiation remains to be fully understood. Increasing evidence indicates noncoding RNAs (ncRNAs) may play important regulatory roles in many physiological and/or pathologic processes...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28656211/notch-signaling-pathway-promotes-osteogenic-differentiation-of-mesenchymal-stem-cells-by-enhancing-bmp9-smad-signaling
#10
Junjie Cao, Yalin Wei, Jing Lian, Lunyun Yang, Xiaoyan Zhang, Jiaying Xie, Qiang Liu, Jinyong Luo, Baicheng He, Min Tang
Notch is an important pathway in that it regulates cell-to-cell signal transduction, which plays an essential role in skeletal remodeling. Bone morphogenetic protein (BMP)9 has been regarded as one of the most efficient BMPs by which to induce osteogenic differentiation in mesenchymal stem cells (MSCs). Understanding the interaction between Notch and BMP9 signaling is a critical issue for optimizing the application of MSCs and BMPs in bone tissue engineering. In the present study, we investigated the role of Notch signaling in the BMP9‑induced osteogenic differentiation of MSCs...
June 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28646109/bone-morphogenetic-protein-9-bmp9-and-bmp10-enhance-tumor-necrosis-factor-%C3%AE-induced-monocyte-recruitment-to-the-vascular-endothelium-mainly-via-activin-receptor-like-kinase-2
#11
Claudia-Gabriela Mitrofan, Sarah L Appleby, Gerard B Nash, Ziad Mallat, Edwin R Chilvers, Paul D Upton, Nicholas W Morrell
Bone morphogenetic proteins 9 and 10 (BMP9/BMP10) are circulating cytokines with important roles in endothelial homeostasis. The aim of this study was to investigate the roles of BMP9 and BMP10 in mediating monocyte-endothelial interactions using an in vitro flow adhesion assay. Herein, we report that whereas BMP9/BMP10 alone had no effect on monocyte recruitment, at higher concentrations both cytokines synergized with tumor necrosis factor-α (TNFα) to increase recruitment to the vascular endothelium. The BMP9/BMP10-mediated increase in monocyte recruitment in the presence of TNFα was associated with up-regulated expression levels of E-selectin, vascular cell adhesion molecule (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) on endothelial cells...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28644396/runx1-plays-an-important-role-in-mediating-bmp9-induced-osteogenic-differentiation-of-mesenchymal-stem-cells-line-c3h10t1-2-murine-multi-lineage-cells-lines-c2c12-and-mefs
#12
Caixia Ji, Xiaohua Liu, Li Xu, Tingting Yu, Chaoqun Dong, Jinyong Luo
As one of the least studied bone morphogenetic proteins (BMPs), BMP9 is highly capable of promoting osteogenic differentiation. However, the underlying mechanism involved remains largely unknown. Recent studies have demonstrated that RUNX1 (runt-related transcription factor 1) is essential in osteoblast/chondrocyte maturation. In this study, we investigated the function of RUNX1 in BMP9-induced osteogenic of murine mesenchymal stem cell line (C3H10T1/2) and murine multi-lineage cell lines (C2C12 and MEFs). Our data showed that BMP9 promoted the endogenous expression of RUNX1 in C3H10T1/2, C2C12 and MEFs...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28632668/low-intensity-pulsed-ultrasound-lipus-promotes-bmp9-induced-osteogenesis-and-suppresses-inflammatory-responses-in-human-periodontal-ligament-derived-stem-cells
#13
Joji Kusuyama, Toshiaki Nakamura, Tomokazu Ohnishi, Nahoko Eiraku, Kazuyuki Noguchi, Tetsuya Matsuguchi
OBJECTIVE: We previously reported that low intensity pulsed ultrasound (LIPUS) promotes marrow stromal cell (MSC) osteogenesis and suppresses the LPS-induced inflammatory response in osteoblasts. Here, we examined the effects of LIPUS on human periodontal ligament-derived stem cells (hPDLSCs) in chronic inflammatory bone disease, such as periodontitis. MATERIALS AND METHODS: hPDLSCs were collected from 3 healthy third molars. hPDLSCs were induced to differentiate by either recombinant BMP2 or BMP9 with or without daily LIPUS treatment (20 min/d)...
July 2017: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/28564608/structural-basis-of-the-human-endoglin-bmp9-interaction-insights-into-bmp-signaling-and-hht1
#14
Takako Saito, Marcel Bokhove, Romina Croci, Sara Zamora-Caballero, Ling Han, Michelle Letarte, Daniele de Sanctis, Luca Jovine
Endoglin (ENG)/CD105 is an essential endothelial cell co-receptor of the transforming growth factor β (TGF-β) superfamily, mutated in hereditary hemorrhagic telangiectasia type 1 (HHT1) and involved in tumor angiogenesis and preeclampsia. Here, we present crystal structures of the ectodomain of human ENG and its complex with the ligand bone morphogenetic protein 9 (BMP9). BMP9 interacts with a hydrophobic surface of the N-terminal orphan domain of ENG, which adopts a new duplicated fold generated by circular permutation...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28527192/in-vitro-evaluation-of-an-injectable-biphasic-calcium-phosphate-bcp-carrier-system-combined-with-recombinant-human-bone-morphogenetic-protein-rhbmp-9
#15
Masako Fujioka-Kobayashi, Benoit Schaller, Yufeng Zhang, Benjamin E Pippenger, Richard J Miron
Bone morphogenetic protein 9 (BMP9) has previously been characterized as the strongest osteoinductive growth factor among the BMP family. The aim of the present study was to evaluate the possibility of combining rhBMP9 with an injectable biphasic calcium phosphate (I-BCP, maxresorb inject®), since I-BCP is an easy to handle biomaterial with ideal properties for bone augmentation procedures. The adsorption potential of rhBMP9 as well as the cell behavior of bone stromal ST2 cells were investigated on cell viability, adhesion, proliferation and osteogenic differentiation for I-BCP combined with/without rhBMP9 in vitro...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28494939/cardiosphere-derived-cells-require-endoglin-for-paracrine-mediated-angiogenesis
#16
Rachael E Redgrave, Simon Tual-Chalot, Benjamin J Davison, Esha Singh, Darroch Hall, Muhammad M Amirrasouli, Derek Gilchrist, Alexander Medvinsky, Helen M Arthur
Clinical trials of stem cell therapy to treat ischemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis, and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific transforming growth factor β (TGFβ) family ligands, including bone morphogenetic protein 9 (BMP9)...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28470873/bmp9-induces-osteogenesis-and-adipogenesis-in-the-immortalized-human-cranial-suture-progenitors-from-the-patent-sutures-of-craniosynostosis-patients
#17
Dongzhe Song, Fugui Zhang, Russell R Reid, Jixing Ye, Qiang Wei, Junyi Liao, Yulong Zou, Jiaming Fan, Chao Ma, Xue Hu, Xiangyang Qu, Liqun Chen, Li Li, Yichun Yu, Xinyi Yu, Zhicai Zhang, Chen Zhao, Zongyue Zeng, Ruyi Zhang, Shujuan Yan, Tingting Wu, Xingye Wu, Yi Shu, Jiayan Lei, Yasha Li, Wenwen Zhang, Jia Wang, Michael J Lee, Jennifer Moriatis Wolf, Dingming Huang, Tong-Chuan He
The cranial suture complex is a heterogeneous tissue consisting of osteogenic progenitor cells and mesenchymal stem cells (MSCs) from bone marrow and suture mesenchyme. The fusion of cranial sutures is a highly coordinated and tightly regulated process during development. Craniosynostosis is a congenital malformation caused by premature fusion of cranial sutures. While the progenitor cells derived from the cranial suture complex should prove valuable for studying the molecular mechanisms underlying suture development and pathogenic premature suture fusion, primary human cranial suture progenitors (SuPs) have limited life span and gradually lose osteoblastic ability over passages...
May 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28470822/pericyte-derived-bone-morphogenetic-protein-4-underlies-white-matter-damage-after-chronic-hypoperfusion
#18
Maiko T Uemura, Masafumi Ihara, Takakuni Maki, Takayuki Nakagomi, Seiji Kaji, Kengo Uemura, Tomohiro Matsuyama, Raj N Kalaria, Ayae Kinoshita, Ryosuke Takahashi
Subcortical small vessel disease (SVD) is characterized by white matter damage resulting from arteriolosclerosis and chronic hypoperfusion. Transforming growth factor beta 1 (TGFB1) is dysregulated in the hereditary SVD, CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy). However, very little is known about the role of the largest group in the TGFB superfamily - the bone morphogenetic proteins (BMPs) - in SVD pathogenesis. The aim of this study was to characterize signaling abnormalities of BMPs in sporadic SVD...
May 4, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28466608/guided-bone-regeneration-with-recombinant-human-bone-morphogenetic-protein-9-loaded-on-either-deproteinized-bovine-bone-mineral-or-a-collagen-barrier-membrane
#19
Nikola Saulacic, Masako Fujioka-Kobayashi, Eizaburo Kobayashi, Benoit Schaller, Richard J Miron
BACKGROUND: Recombinant human bone morphogenetic protein 9 (rhBMP9) has been considered the most osteoinductive growth factor of the BMP-family and has much translation potential for guided bone regeneration (GBR) procedures. PURPOSE: The aim of this study was to compare bone formation using rhBMP9 loaded with different carrier systems including deprotenized bovine bone mineral (BioOss, BO) or collagen barrier membranes (BioGide, BG) in a rabbit GBR model. MATERIALS AND METHODS: rhBMP9 was loaded either on BO; named BO/BMP9, or BG; named BG/BMP9 to investigate the better carrier system for rhBMP9...
May 2, 2017: Clinical Implant Dentistry and related Research
https://www.readbyqxmd.com/read/28447742/bone-morphogenetic-protein-9-stimulates-callus-formation-in-osteoporotic-rats-during-fracture-healing
#20
Xing Wang, Jun Huang, Fan Huang, Jian-Chun Zong, Xi Tang, Yang Liu, Qiong-Fang Zhang, Yang Wang, Liang Chen, Liang-Jun Yin, Bai-Cheng He, Zhong-Liang Deng
Fracture healing involves the coordinated actions of multiple cytokines. Bone morphogenetic protein 9 (BMP9) is an important factor in bone formation. The present study aimed to investigate the osteogenic potential of bone marrow stem cells (BMSCs) in response to adenoviral (Ad)BMP9, and the early fracture repair properties of AdBMP9 in surgically‑created fractures in osteoporotic rats. Alkaline phosphatase (ALP) activity was assayed and matrix mineralization was examined by Alizarin Red S staining. mRNA and protein expression levels of BMP9, runt‑related transcription factor 2 (RUNX2) and type 1 collagen (COL‑1) were detected in vitro and in vivo...
May 2017: Molecular Medicine Reports
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