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https://www.readbyqxmd.com/read/28926103/fam20c-regulates-osteoblast-behaviors-and-intracellular-signaling-pathways-in-a-cell-autonomous-manner
#1
Chao Liu, Hua Zhang, Priyam Jani, Xiaofang Wang, Yongbo Lu, Nan Li, Jing Xiao, Chunlin Qin
Recent studies indicate that Family with sequence similarity 20 member C (FAM20C) catalyzes the phosphorylation of secreted proteins, and participates in a variety of biological processes, including cell proliferation, migration, mineralization and phosphate homeostasis. To explore the local influences of FAM20C on osteoblast, Fam20c-deficient osteoblasts were generated by treating the immortalized Fam20c(f/f) osteoblasts with CMV-Cre-IRES-EGFP lentivirus. Compared with the normal Fam20c(f/f) osteoblasts, the expression of Bone sialoprotein (Bsp), Osteocalcin (Ocn), Fibroblast growth factor 23 (Fgf23) and transcription factors that promote osteoblast maturation were up-regulated in the Fam20c-deficient osteoblasts...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28926099/anti-osteoporosis-activity-of-sanguinarine-in-preosteoblast-mc3t3-e1-cells-and-an-ovariectomized-rat-model
#2
Fuzhan Zhang, Jile Xie, Genlin Wang, Ge Zhang, Huilin Yang
Sanguinarine, a benzophenanthridine alkaloid, has been previously demonstrated to exert antimicrobial, anti-inflammatory and anti-tumor activities. A previous study has identified Sanguinarine as a potential drug candidate for osteoporosis treatment by computational bioinformatics analysis. This study further evaluated the effects of Sanguinarine on the differentiation of murine preosteoblast MC3T3-E1 cells and its anti-osteoporosis activity in an ovarietomized rat model. Sanguinarine treatment (0.25, 0.5, 1 and 2 µM) of MC3T3-E1 cells significantly increased alkaline phosphatase (ALP) activity and the phoshporalyation of AMP-activated protein kinase α subunit (AMPKα), but did not affect cell proliferation...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28923783/bmp7-induced-pten-inhibits-akt-and-prevents-renal-fibrosis
#3
Debra F Higgins, Leah Ewart, Enda Masterson, Sadhbh Tennant, Gleb Grebnev, Marco Prunotto, Sylvia Pomposiello, Karin Conde-Knape, Finian M Martin, Catherine Godson
Bone morphogenetic protein-7 (BMP-7) counteracts pro-fibrotic effects of TGFβ1 in cultured renal cells and protects from fibrosis in acute and chronic renal injury models. Using the unilateral ureteral obstruction (UUO) model of chronic renal fibrosis, we investigated the effect of exogenous-rhBMP-7 on pro-fibrotic signaling pathways mediated by TGFβ1 and hypoxia. Mice undergoing UUO were treated with vehicle or rhBMP-7 (300μg/kg i.p.) every other day for eight days and kidneys analysed for markers of fibrosis and SMAD, MAPK, and PI3K signaling...
September 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28921936/sprouty2-is-involved-in-the-control-of-osteoblast-proliferation-and-differentiation-through-the-fgf-and-bmp-signaling-pathways
#4
Takaharu Taketomi, Tomohiro Onimura, Daigo Yoshiga, Daichi Muratsu, Terukazu Sanui, Takao Fukuda, Jingo Kusukawa, Seiji Nakamura
Fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) play essential roles in bone formation and osteoblast activity through the extracellular signal regulated kinase 1/2 (ERK1/2) and Smad pathways. Sprouty family members are intracellular inhibitors of the FGF signaling pathway, and four orthologs of Sprouty have been identified in mammals. In vivo analyses have revealed that Sprouty2 is associated with bone formation. However, the mechanism by which the Sprouty family controls bone formation has not been clarified...
September 16, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28903487/from-the-cover-arsenic-induces-hippocampal-neuronal-apoptosis-and-cognitive-impairments-via-an-up-regulated-bmp2-smad-dependent-reduced-bdnf-trkb-signaling-in-rats
#5
Rukmani Pandey, Vipin Rai, Juhi Mishra, Kapil Mandrah, Somendu Kumar Roy, Sanghamitra Bandyopadhyay
Arsenic promotes hippocampal neuronal damage inducing cognitive impairments. However, mechanism arbitrating arsenic-mediated cognitive deficits remains less-known. Here, we identified that chronic exposure to environmentally relevant doses of arsenic increased apoptosis, characterized by caspase-3 activation, poly(ADP-ribose) polymerase cleavage and Terminal deoxynucleotidyl transferase dUTP nick-end labeling of rat hippocampal neurons, marked by NeuN. Investigating apoptotic mechanism through invivo and invitro studies revealed that arsenic promoted bone morphogenetic protein-2 (BMP2) expression, supported by increased BMP-receptor2 (BMPR2) and p-Smad1/5 in hippocampal neurons...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28893092/salvianolic-acid-a-a-component-of-salvia-miltiorrhiza-attenuates-endothelial-mesenchymal-transition-of-hpaecs-induced-by-hypoxia
#6
Tianyi Yuan, Yucai Chen, Huifang Zhang, Lianhua Fang, Guanhua Du
Salvianolic acid A (SAA), a polyphenols acid, is a bioactive ingredient from a traditional Chinese medicine called Dan shen (Salvia Miltiorrhiza Bunge). According to previous studies, it was shown to have various effects such as anti-oxidative stress, antidiabetic complications and antipulmonary hypertension. This study aimed to investigate the effect of SAA on pulmonary arterial endothelial-mesenchymal transition (EndoMT) induced by hypoxia and the underlying mechanisms. Primary cultured human pulmonary arterial endothelial cells (HPAECs) were exposed to 1% O2 for 48[Formula: see text]h with or without SAA treatment...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28881580/selective-compounds-enhance-osteoblastic-activity-by-targeting-hect-domain-of-ubiquitin-ligase-smurf1
#7
Yuan Zhang, Cheng Wang, Yu Cao, Yongqing Gu, Lingqiang Zhang
The HECT-type ubiquitin ligase Smurf1 (Smad ubiquitination regulatory factor-1) plays the prominent role in regulation of bone formation, embryonic development, and tumorigenesis by directing the ubiquitin-proteasomal degradation of specific targets. In contrast with RING-type E3s, the catalytic HECT domain of Smurf1 firstly binds to and then transfers ubiquitin (Ub) molecules onto the substrates. The Smurf1-Ub interaction is required for Smurf1 catalytic ligase activity to promote substrate degradation. However, so far specific regulators or compounds controlling Smurf1-Ub interaction and the ligase activity have not been identified...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28852126/decrease-of-fstl1-bmp4-smad-signaling-predicts-poor-prognosis-in-lung-adenocarcinoma-but-not-in-squamous-cell-carcinoma
#8
Jean Chiou, Chia-Yi Su, Yi-Hua Jan, Chih-Jen Yang, Ming-Shyan Huang, Yung-Luen Yu, Michael Hsiao
Follistatin-related protein 1 (FSTL1) plays a critical role in lung development through regulating BMP4-p-Smad1/5/8-Smad4 pathway. Regarding that many developmental pathways in embryogenesis are dysregulated in cancer, we aim to unravel the role of FSTL1-BMP4-Smad pathway in lung cancer. Our results showed low FSTL1 immunoexpression was significantly correlated with poor prognosis while patients with low BMP4 or low Smad4 immunoexpression showed a trend toward poor prognosis. When stratified by different histological types, low FSTL1, BMP4, and Smad4 expression retained their trends in predicting poor prognosis in lung adenocarcinoma (LUAD) but not in lung squamous cell carcinoma (SCC)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838258/the-protective-effects-of-bone-morphogenetic-protein-7-against-epithelial-injury-and-matrix-metalloproteases-upregulation-induced-by-silica-in-vitro
#9
D Liang, G An, Z Zhu, Y Wang, G Yang, X Li, P Niu, L Chen, L Tian
OBJECTIVE: We investigate the effects of bone morphogenetic protein-7 (BMP-7) on models with silica-induced and macrophage-mediated fibrosis and its possible mechanisms in vitro. METHODS: Rat alveolar II epithelial (RLE-6TN) cells were incubated with the supernatant of mouse macrophage-like cells (RAW264.7) and treated with 0, 25, 50, and 100 μg/mL silica. Using Western blotting, the epithelial markers (surfactant proteins-C and E-cadherin) and the mesenchymal markers (fibronectin (FN) and viminten (Vim)) were detected...
September 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28829997/msx2-is-required-for-vascular-smooth-muscle-cells-osteoblastic-differentiation-but-not-calcification-in-insulin-resistant-ob-ob-mice
#10
Maria Claudina Andrade, Luciana S Carmo, Elisangela Farias-Silva, Marcel Liberman
BACKGROUND AND AIMS: Obesity and diabetes potentiate vascular calcification by increasing vascular smooth muscle cells osteoblastic differentiation mediated by the transcription factor Msx2 and bone morphogenetic protein-2 signaling. However, Bmp-2/Msx2 crosstalk to induce VSMC osteogenic phenotype transition and calcification is poorly understood in diabetes. We aimed to investigate mechanisms underlying Bmp-2-driven VSMC osteogenic differentiation and calcification in leptin-deficient ob/ob mice...
July 29, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28815657/celecoxib-inhibits-osteoblast-differentiation-independent-of-cyclooxygenase-activity
#11
Atsushi Matsuyama, Sen Higashi, Saori Tanizaki, Takahiko Morotomi, Ayako Washio, Tomoko Ohsumi, Chiaki Kitamura, Hiroshi Takeuchi
Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects primarily by inhibiting the activity of cyclooxygenase (COX), thus suppressing prostaglandin synthesis. Some NSAIDs are known to perform functions other than pain control, such as suppressing tumour cell growth, independent of their COX-inhibiting activity. To identify NSAIDs with COX-independent activity, we examined various NSAIDs for their ability to inhibit osteoblastic differentiation using the mouse pre-osteoblast cell line MC3T3-E1. Only celecoxib and valdecoxib strongly inhibited osteoblastic differentiation, and this effect was not correlated with COX-inhibiting activity...
August 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#12
Su Jung Bae, Hye Joo Kim, Hee Yeon Won, Yong Ki Min, Eun Sook Hwang
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812969/functional-expression-of-bmp7-receptors-in-oral-epithelial-cells-interleukin-17f-production-in-response-to-bmp7
#13
Kensuke Nishio, Yasumasa Ozawa, Hisanori Ito, Takashi Kifune, Tatsuya Narita, Toshimitsu Iinuma, Nobuhito Gionhaku, Masatake Asano
BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily. Recently, BMP7 has been demonstrated to be produced by salivary glands and contribute to embryonic branching in mice. The BMP7 in saliva is thought to be delivered to the oral cavity and is expected to contact with stratified squamous epithelial cells which line the surface of oral mucosa. In this study, we attempted to investigate the effects of BMP7 on oral epithelial cells...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#14
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#15
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In our previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition state (EMT) and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of HCV core expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28782519/identification-of-novel-alk2-inhibitors-and-their-effect-on-cancer-cells
#16
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...
August 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28761062/t2diacod-a-gene-atlas-of-type-2-diabetes-mellitus-associated-complex-disorders
#17
Jyoti Rani, Inna Mittal, Atreyi Pramanik, Namita Singh, Namita Dube, Smriti Sharma, Bhanwar Lal Puniya, Muthukurussi Varieth Raghunandanan, Ahmed Mobeen, Srinivasan Ramachandran
We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus. They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression. The database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760815/endothelial-cells-respond-to-the-direction-of-mechanical-stimuli-through-smad-signaling-to-regulate-coronary-artery-size
#18
Aruna Poduri, Brian Raftrey, Andrew H Chang, Siyeon Rhee, Mike Van, Kristy Red-Horse
How mechanotransduction intersects with chemical and transcriptional factors to shape organogenesis is an important question in developmental biology. This is particularly relevant to the cardiovascular system, which uses mechanical signals from flowing blood to stimulate cytoskeletal and transcriptional responses that form a highly efficient vascular network. Using this system, artery size and structure are tightly regulated, but the underlying mechanisms are poorly understood. Here, we demonstrate that deletion of Smad4 increased the diameter of coronary arteries during embryonic development, a phenotype that followed the initiation of blood flow...
July 31, 2017: Development
https://www.readbyqxmd.com/read/28755405/serum-ifn-%C3%AE-predicts-the-therapeutic-effect-of-mesenchymal-stem-cells-transplantation-in-systemic-lupus-erythematosus-patients
#19
Dandan Wang, Shiying Wang, Saisai Huang, Zhuoya Zhang, Xinran Yuan, Xuebing Feng, Liwei Lu, Lingyun Sun
Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) show immunoregulatory properties on various immune cells and display therapeutic effects on various autoimmune diseases such as systemic lupus erythematosus (SLE). The aim of this study was to investigate the effect of the SLE environment on UC MSCs and to identify a potential serum biomarker to predict the therapeutic effect. UC MSCs were cocultured with peripheral blood mononuclear cells (PBMCs) from active lupus patients, and the proliferation, apoptosis and surface markers of UC MSCs were observed...
September 2017: Stem Cells Translational Medicine
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
#20
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
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