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https://www.readbyqxmd.com/read/28874783/hyperactive-tgf-%C3%AE-signaling-in-smooth-muscle-cells-exposed-to-hiv-protein-s-and-cocaine-role-in-pulmonary-vasculopathy
#1
Pranjali Dalvi, Himanshu Sharma, Tomara Konstantinova, Miles Sanderson, Amy O' Brien-Ladner, Navneet K Dhillon
We earlier demonstrated synergistic increase in the proliferation of pulmonary smooth muscle cells on exposure to HIV-proteins and/or cocaine due to severe down-modulation of bone morphogenetic protein receptor (BMPR) axis: the anti-proliferative arm of TGF-β super family of receptors. Here, now we demonstrate the effect of HIV-Tat and cocaine on the proliferative TGF-β signaling cascade. We observed a significant increase in the secretion of TGF-β1 ligand along with enhanced protein expression of TGFβ Receptor (TGFβR)-1, TGFβR-2 and phosphorylated SMAD2/3 in human pulmonary arterial smooth muscle cells on treatment with cocaine and Tat...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28869829/strontium-doping-promotes-bioactivity-of-rhbmp-2-upon-calcium-phosphate-cement-via-elevated-recognition-and-expression-of-bmpr-ia
#2
Baolin Huang, Yu Tian, Wenjing Zhang, Yifan Ma, Yuan Yuan, Changsheng Liu
Preserving and improving osteogenic activity of bone morphogenetic protein-2 (BMP-2) upon implants remains one of the key limitations in bone regeneration. With calcium phosphate cement (CPC) as model, we have developed a series of strontium (Sr)-doped CPC (SCPC) to address this issue. The effects of fixed Sr on the bioactivity of recombinant human BMP-2 (rhBMP-2) as well as the underlying mechanism were investigated. The results suggested that the rhBMP-2-induced osteogenic activity was significantly promoted upon SCPCs, especially with a low amount of fixed Sr (SrCO3 content <10wt%)...
June 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28716575/strategic-targeting-of-multiple-bmp-receptors-prevents-trauma-induced-heterotopic-ossification
#3
Shailesh Agarwal, Shawn J Loder, Christopher Breuler, John Li, David Cholok, Cameron Brownley, Jonathan Peterson, Hsiao H Hsieh, James Drake, Kavitha Ranganathan, Yashar S Niknafs, Wenzhong Xiao, Shuli Li, Ravindra Kumar, Ronald Tompkins, Michael T Longaker, Thomas A Davis, Paul B Yu, Yuji Mishina, Benjamin Levi
Trauma-induced heterotopic ossification (tHO) is a condition of pathologic wound healing, defined by the progressive formation of ectopic bone in soft tissue following severe burns or trauma. Because previous studies have shown that genetic variants of HO, such as fibrodysplasia ossificans progressiva (FOP), are caused by hyperactivating mutations of the type I bone morphogenetic protein receptor (T1-BMPR) ACVR1/ALK2, studies evaluating therapies for HO have been directed primarily toward drugs for this specific receptor...
August 2, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28705683/periodontal-ligament-fibroblasts-as-a-cell-model-to-study-osteogenesis-and-osteoclastogenesis-in-fibrodysplasia-ossificans-progressiva
#4
Teun J de Vries, Ton Schoenmaker, Dimitra Micha, Jolanda Hogervorst, Siham Bouskla, Tim Forouzanfar, Gerard Pals, Coen Netelenbos, E Marelise W Eekhoff, Nathalie Bravenboer
Fibrodysplasia Ossificans Progressiva (FOP) is a progressive disease characterized by periods of heterotopic ossification of soft connective tissues, including ligaments. Though progress has been made in recent years in unraveling the underlying mechanism, patient-derived cell models are necessary to test potential treatment options. Periodontal ligament fibroblasts (PLF) from extracted teeth can be used to study deviant bone modeling processes in vitro since these cells are derived from genuine ligaments. They further provide a tool to study the hitherto unknown role of the bone morphogenesis protein receptor type 1 (BMPR-1) Activin A type 1 receptor ACVR1-R206H mutation in osteoclastogenesis...
July 10, 2017: Bone
https://www.readbyqxmd.com/read/28687190/a-synthetic-bmp-2-mimicking-peptide-induces-glioblastoma-stem-cell-differentiation
#5
Elena Rampazzo, Monica Dettin, Francesca Maule, Alessandra Scabello, Luisa Calvanese, Gabriella D'Auria, Lucia Falcigno, Elena Porcù, Annj Zamuner, Alessandro Della Puppa, Daniele Boso, Giuseppe Basso, Luca Persano
BACKGROUND: Glioblastoma (GBM) is the most aggressive type of primary brain tumor, characterized by the intrinsic resistance to chemotherapy due to the presence of a highly aggressive Cancer Stem Cell (CSC) sub-population. In this context, Bone Morphogenetic Proteins (BMPs) have been demonstrated to induce CSC differentiation and to sensitize GBM cells to treatments. METHODS: The BMP-2 mimicking peptide, named GBMP1a, was synthesized on solid-phase by Fmoc chemistry...
September 2017: Biochimica et Biophysica Acta
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
#6
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/28585345/genetic-screening-of-fecb-fecx-g-and-fecx-i-mutations-and-their-linkage-with-litter-size-in-barki-and-rahmani-sheep-breeds
#7
A S El-Seedy, N M Hashem, K M El-Azrak, Anm Nour El-Din, T A Ramadan, T A Taha, M H Salem
Characterization of fecundity genes offers the opportunity to improve production efficiency, and the consequent increase in litter size in livestock industry, through utilizing them in breeding programs. The main objective of this study was to detect the BMPR-IB, BMP15 and GDF9 gene mutations and to investigate whether these mutations are associated with litter size in Egyptian sheep breeds. To achieve this goal, 73 adult ewes representing Barki (n = 33) and Rahmani (n = 40) breeds were used. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) screening approach was used to detect the presence of FecB, FecX(G) and FecX(I) mutations in the two selected breeds...
June 5, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28481944/a-consistent-and-potentially-exploitable-response-during-chondrogenesis-of-mesenchymal-stem-cells-from-osteoarthritis-patients-to-the-protein-encoded-by-the-susceptibility-gene-gdf5
#8
Madhushika Ratnayake, Maria Tselepi, Robert Bloxham, Frank Plöger, Louise N Reynard, John Loughlin
Osteoarthritis (OA) is a common joint disease characterised by the focal loss of the protective cartilage layer at the ends of the bones. It is painful, disabling, multifactorial and polygenic. The growth differentiation factor 5 gene GDF5 was one of the first reported OA susceptibility signals that showed consistent association to OA, with the transcript single nucleotide polymorphism (SNP) rs143383 demonstrating association in Asians and Europeans. The functional effect of the signal is reduced expression of the gene...
2017: PloS One
https://www.readbyqxmd.com/read/28423564/hypermethylation-of-the-chrdl1-promoter-induces-proliferation-and-metastasis-by-activating-akt-and-erk-in-gastric-cancer
#9
Yao-Fei Pei, Ya-Jing Zhang, Yao Lei, Ding-Wei Wu, Tong-Hui Ma, Xi-Qiang Liu
CHRDL1 (Chordin-like 1) is a secreted protein that acts as an antagonist of bone morphogenetic protein (BMP). BMP plays a role as an activator of BMP receptor II (BMPR II), which mediates extracellular to intracellular signal transmission and is involved in carcinogenesis and metastasis. Herein, we report that CHRDL1 expression was significantly down-regulated in gastric cancer tissues and associated with poor survival. Clinic-pathological parameters demonstrated a close relationship between low CHRDL1 expression and metastasis...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28287559/rapid-isolation-of-bmpr-ib-adipose-derived-stromal-cells-for-use-in-a-calvarial-defect-healing-model
#10
Clement D Marshall, Elizabeth R Zielins, Elizabeth A Brett, Charles P Blackshear, Michael S Hu, Tripp Leavitt, Leandra A Barnes, H Peter Lorenz, Michael T Longaker, Derrick C Wan
Invasive cancers, major injuries, and infection can cause bone defects that are too large to be reconstructed with preexisting bone from the patient's own body. The ability to grow bone de novo using a patient's own cells would allow bony defects to be filled with adequate tissue without the morbidity of harvesting native bone. There is interest in the use of adipose-derived stromal cells (ASCs) as a source for tissue engineering because these are obtained from an abundant source: the patient's own adipose tissue...
February 24, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28188849/endocytosis-contributes-to-bmp2-induced-smad-signalling-and-neuronal-growth
#11
Shane V Hegarty, Aideen M Sullivan, Gerard W O'Keeffe
Bone morphogenetic protein 2 (BMP2) is a neurotrophic factor which induces the growth of midbrain dopaminergic (DA) neurons in vitro and in vivo, and its neurotrophic effects have been shown to be dependent on activation of BMP receptors (BMPRs) and Smad 1/5/8 signalling. However, the precise intracellular cascades that regulate BMP2-BMPR-Smad-signalling-induced neurite growth remain unknown. Endocytosis has been shown to regulate Smad 1/5/8 signalling and differentiation induced by BMPs. However, these studies were carried out in non-neural cells...
March 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28188131/momelotinib-inhibits-acvr1-alk2-decreases-hepcidin-production-and-ameliorates-anemia-of-chronic-disease-in-rodents
#12
Malte Asshoff, Verena Petzer, Matthew R Warr, David Haschka, Piotr Tymoszuk, Egon Demetz, Markus Seifert, Wilfried Posch, Manfred Nairz, Pat Maciejewski, Peter Fowles, Christopher J Burns, Gregg Smith, Kay-Uwe Wagner, Guenter Weiss, J Andrew Whitney, Igor Theurl
Patients with myelofibrosis (MF) often develop anemia and frequently become dependent on red blood cell transfusions. Results from a phase 2 study for the treatment of MF with the Janus kinase 1/2 (JAK1/2) inhibitor momelotinib (MMB) demonstrated that MMB treatment ameliorated anemia, which was unexpected for a JAK1/2 inhibitor, because erythropoietin-mediated JAK2 signaling is essential for erythropoiesis. Using a rat model of anemia of chronic disease, we demonstrated that MMB treatment can normalize hemoglobin and red blood cell numbers...
March 30, 2017: Blood
https://www.readbyqxmd.com/read/28108032/disruption-of-the-sheep-bmpr-ib-gene-by-crispr-cas9-in-in%C3%A2-vitro-produced-embryos
#13
Xuemei Zhang, Wenrong Li, Yangsheng Wu, Xinrong Peng, Bian Lou, Liqin Wang, Mingjun Liu
BMPR-IB (also known as FecB) is a key candidate gene for the genetic control of sheep reproductive performance. Loss-of-function mutations in the sheep BMPR-IB gene lead to an increase in ovulation rate and consequently larger litter size. However, the BMPR-IB gene has been identified in only a few sheep breeds. To improve sheep reproduction through modification of the BMPR-IB gene, we designed an sgRNA to target the sheep BMPR-IB gene by using the CRISPR/Cas9 system. First, we performed gene editing by injecting Cas9/sgRNA into the cytoplasm of one-cell fertilized eggs...
March 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/27920998/short-term-organ-culture-of-mouse-ovary-in-the-medium-supplemented-with-bone-morphogenetic-protein-15-and-follicle-stimulating-hormone-a-morphological-hormonal-and-molecular-study
#14
Mojdeh Salehnia, Mojdeh Pajokh, Nassim Ghorbanmehr
BACKGROUND: Bone morphogenetic protein 15 (BMP15) is a growth factor derived from oocyte and is essential for in vivo ovarian follicular growth and in this study, its effects on the improvement of growth and development of follicles during in vitro culture of neonatal mouse ovaries was investigated. METHODS: Two week old mice were cultured for 7 days in the basic culture media with or without follicle stimulating hormone (FSH) and BMP15 as four experimental groups; FSH(-)/BMP15(-), FSH(+)/BMP15(-), FSH(-)/BMP15(+) and FSH(+)/BMP15(+)...
October 2016: Journal of Reproduction & Infertility
https://www.readbyqxmd.com/read/27780042/immunoexpression-of-bmp-2-and-bmp-4-and-their-receptors-bmpr-ia-and-bmpr-ii-in-ameloblastomas-and-adenomatoid-odontogenic-tumors
#15
Marcelo Anderson Barbosa Nascimento, Cassiano Francisco Weege Nonaka, Carlos Augusto Galvão Barboza, Roseana de Almeida Freitas, Leão Pereira Pinto, Lélia Batista de Souza
OBJECTIVES: The present study evaluated the immunohistochemical expression of BMP-2 and BMP-4 and of their receptors (BMPR-IA and BMPR-II) in solid ameloblastoma (SA), unicystic ameloblastoma (UA) and adenomatoid odontogenic tumor (AOT) in order to obtain a better understanding of their role in the development and biological behavior of these tumors. DESIGN: This study analyzed these proteins in 30 cases of SA, 10 cases of UA, and 30 cases of AOT. Immunoexpression was evaluated in the parenchyma and stroma by attributing the following scores: 0, no stained cells; 1, ≤10%; 2, >10% and ≤25%; 3, >25% and ≤50%; 4, >50% and ≤75%...
January 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/27754275/sy-18-1-translational-research-in-pah
#16
Wook-Jin Chung
Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome...
September 2016: Journal of Hypertension
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
#17
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/27720933/activation-of-the-pro-migratory-bone-morphogenetic-protein-receptor-1b-gene-in-human-mda-mb-468-triple-negative-breast-cancer-cells-that-over-express-cyp2j2
#18
Sarah E Allison, Yongjuan Chen, Nenad Petrovic, Stefanie Zimmermann, Bjoern Moosmann, Mirko Jansch, Pei H Cui, Colin R Dunstan, Peter I Mackenzie, Michael Murray
Secondary metastases are the leading cause of mortality in patients with breast cancer. Cytochrome P450 (CYP) 2J2 (CYP2J2) is upregulated in many human tumors and generates epoxyeicosanoids from arachidonic acid that promote tumorigenesis and metastasis, but at present there is little information on the genes that mediate these actions. In this study MDA-MB-468 breast cancer cells were stably transfected with CYP2J2 (MDA-2J2 cells) and Affymetrix microarray profiling was undertaken. We identified 182 genes that were differentially expressed in MDA-2J2 cells relative to control (MDA-CTL) cells (log[fold of control] ≥2)...
October 5, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27660075/hnf-4alpha-negatively-regulates-hepcidin-expression-through-bmpr1a-in-hepg2-cells
#19
Wencai Shi, Heyang Wang, Xuan Zheng, Xin Jiang, Zheng Xu, Hui Shen, Min Li
Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4α (HNF-4α) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4α on hepcidin expression was observed by transfecting specific HNF-4α small interfering RNA (siRNA) or plasmids into HepG2 cells...
April 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/27643272/sy-18-1-translational-research-in-pah
#20
Wook-Jin Chung
Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome...
September 2016: Journal of Hypertension
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