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BMP AND smad

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https://www.readbyqxmd.com/read/29339534/inactivating-mutations-in-drosha-mediate-vascular-abnormalities-similar-to-hereditary-hemorrhagic-telangiectasia
#1
Xuan Jiang, Whitney L Wooderchak-Donahue, Jamie McDonald, Prajakta Ghatpande, Mai Baalbaki, Melissa Sandoval, Daniel Hart, Hilary Clay, Shaun Coughlin, Giorgio Lagna, Pinar Bayrak-Toydemir, Akiko Hata
The transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMP) family of cytokines critically regulates vascular morphogenesis and homeostasis. Impairment of TGF-β or BMP signaling leads to heritable vascular disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-β and BMP pathway through interaction with Smads and their joint control of gene expression through miRNAs. We report that mice lacking Drosha in the vascular endothelium developed a vascular phenotype resembling HHT that included dilated and disorganized vasculature, arteriovenous fistulae, and hemorrhages...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29339189/magnetic-nanoparticles-modified-porous-scaffolds-for-bone-regeneration-and-photothermal-therapy-against-tumors
#2
Jia-Wei Lu, Fan Yang, Qin-Fei Ke, Xue-Tao Xie, Ya-Ping Guo
For effectively treating tumor related-bone defects, design and fabrication of multifunctional biomaterials still remain a great challenge. Herein, we firstly fabricated magnetic SrFe12O19 nanoparticles modified-mesoporous bioglass (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and antitumor function. The as-produced magnetic field from MBCS promoted the expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the new bone regeneration by activated BMP-2/Smad/Runx2 pathway...
January 12, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29328402/mir%C3%A2-203%C3%A2-3p-participates-in-the-suppression-of-diabetes%C3%A2-associated-osteogenesis-in-the-jaw-bone-through-targeting-smad1
#3
Yuying Tang, Leilei Zheng, Jie Zhou, Yang Chen, Lan Yang, Feng Deng, Yun Hu
Certain microRNAs (miRs) have important roles in the maintenance of bone development and metabolism, and a variety of miRs are known to be deregulated in diabetes. The present study investigated the role of miR‑203‑3p in the regulation of bone loss by assessing jaw bones of a rat model of type 2 diabetes. The results indicated that miR‑203‑3p inhibited osteogenesis in the jaws of diabetic rats and in rat bone marrow mesenchymal stem cells cultured in high‑glucose medium. A luciferase re-porter assay was used to verify the bioinformatics prediction that miR‑203‑3p targets the 3'‑untranslated region of Smad1, which is an important mediator of the bone morphogenetic protein (BMP)/Smad pathway...
January 9, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29324800/hepcidin-deficiency-and-iron-deficiency-do-not-alter-tuberculosis-susceptibility-in-a-murine-m-tb-infection-model
#4
Rachel Harrington-Kandt, Elena Stylianou, Lucy A Eddowes, Pei Jin Lim, Lisa Stockdale, Nawamin Pinpathomrat, Naomi Bull, Janet Pasricha, Marta Ulaszewska, Yulia Beglov, Sophie Vaulont, Hal Drakesmith, Helen McShane
Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection...
2018: PloS One
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#5
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29318958/a-cell-engineered-small-intestinal-submucosa-based-bone-mimetic-construct-for-bone-regeneration
#6
Mei Li, Chi Zhang, Yuxing Mao, Yi Zhong, Jiyuan Zhao
Extracellular matrix (ECM)-ornamented biomaterials have attracted attention due to their high potential to improve the bio-functionality of original materials. It is thought that ECM with a bone mimetic microenvironment generated by the specific induction of osteoblasts would be more beneficial for bone regeneration than regular ECM. In this study, we developed an osteogenic and mineralized ECM construct (Os/M-ECM-SIS) under the guidance of osteoblasts on a small intestinal submucosa (SIS) scaffold co-treated with icariin and calcium...
January 10, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29317497/identification-of-direct-negative-crosstalk-between-the-slit2-and-bone-morphogenetic-protein-gremlin-signaling-pathways
#7
Kathleen E Tumelty, Nathan Higginson-Scott, Xueping Fan, Piyush Bajaj, Kelly M Knowlton, Michael Shamashkin, Anthony J Coyle, Weining Lu, Stephen P Berasi
Slit guidance ligand 2 (SLIT2) is a large, secreted protein which binds roundabout (ROBO) receptors on multiple cell types including neurons and kidney podocytes. SLIT2-ROBO2 mediated signaling regulates neuronal migration and ureteric bud (UB) outgrowth during kidney development as well as glomerular filtration in adult kidneys. Additionally, SLIT2 binds Gremlin, an antagonist of bone morphogenetic proteins (BMPs), and BMP-Gremlin signaling also regulates UB formation. However, direct crosstalk between the ROBO2-SLIT2 and BMP-Gremlin signaling pathways has not been established...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29317485/meis1-coordinates-cerebellar-granule-cell-development-by-regulating-pax6-transcription-bmp-signaling-and-atoh1-degradation
#8
Tomoo Owa, Shinichiro Taya, Satoshi Miyashita, Mariko Yamashita, Toma Adachi, Koyo Yamada, Miwa Yokoyama, Shogo Aida, Tomoki Nishioka, Yukiko U Inoue, Ryo Goitsuka, Takuro Nakamura, Takayoshi Inoue, Kozo Kaibuchi, Mikio Hoshino
Cerebellar granule cell precursors (GCPs) and granule cells (GCs) represent good models to study neuronal development. Here we report that the transcription factor, Meis1, plays pivotal roles to regulate mouse GC development. We found that Meis1 is expressed in granule cell lineage cells and astrocytes in the cerebellum during development. Targeted disruption of the Meis1 gene specifically in the GC lineage resulted in smaller cerebella with disorganized lobules. Knockdown/knockout experiments for Meis1 as well as in vitro assays show that Meis1 binds to an upstream sequence of Pax6 to enhance its transcription in GCPs/GCs and further suggested that the Meis1-Pax6 cascade regulates morphology of GCPs/GCs during development...
January 9, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29312637/notch-signaling-negatively-regulates-bmp9-induced-osteogenic-differentiation-of-mesenchymal-progenitor-cells-by-inhibiting-junb-expression
#9
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
https://www.readbyqxmd.com/read/29279455/exogenous-bmp-7-facilitates-the-recovery-of-cardiac-function-after-acute-myocardial-infarction-through-counteracting-tgf-%C3%AE-1-signaling-pathway
#10
Yalei Jin, Xinyao Cheng, Jinping Lu, Xia Li
Myocardial fibrosis after acute myocardial infarction (AMI) is one of the main causes of myocardial remodeling and heart function abnormalities. Bone morphogenetic protein-7 (BMP-7) has been reported to play essential roles in anti-fibrosis. In this study, we demonstrated the role of exogenous BMP-7 on myocardial fibrosis and heart function recovery after AMI. A rat model of AMI was established via ligation of the left anterior descending coronary artery (LAD). Twenty rats were grouped into sham group which underwent chest open operation, but did not receive LAD ligation...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29275289/role-of-fluoride-induced-histone-trimethylation-in-development-of-skeletal-fluorosis
#11
Atul P Daiwile, Saravanadevi Sivanesan, Prashant Tarale, Pravin K Naoghare, Amit Bafana, Devendra Parmar, Krishnamurthi Kannan
Chronic exposure to fluoride has been associated with the development of skeletal fluorosis. Limited reports are available on fluoride induced histone modification. However, the role of histone modification in the pathogenesis of skeletal fluorosis is not investigated. In the present study, we have investigated the role of fluoride induced histone modification on fluorosis development using human osteosarcoma (HOS) cell line. The expression of histone methyltransferases (EHMT1 and EHZ2) and level of global histone trimethylation (H3K9 and H3K27) have been assessed and observed to be increased significantly after fluoride exposure (8 mg/L)...
December 17, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/29259034/ablation-of-the-mammalian-lectin-galectin-8-induces-bone-defects-in-mice
#12
Yaron Vinik, Hadas Shatz-Azoulay, Sahar Hiram-Bab, Leonid Kandel, Yankel Gabet, Gurion Rivkin, Yehiel Zick
Mice overexpressing galectin-8 [gal-8 transgenic (Tg)], a secreted mammalian lectin, exhibit enhanced bone turnover and reduced bone mass, similar to cases of postmenopausal osteoporosis. Here, we show that gal-8 knockout (KO) mice have increased bone mass accrual at a young age but exhibit accelerated bone loss during adulthood. These phenotypes can be attributed to a gal-8-mediated increase in receptor activator of NF-κB ligand (RANKL) expression that promotes osteoclastogenesis, combined with direct inhibition of osteoblasts differentiation, evident by reduced bone morphogenetic protein (BMP) signaling, reduced phosphorylation of receptor regulated mothers against decapentaplegic homolog (R-SMAD) and reduced expression of osteoblasts differentiation markers osterix, osteocalcin, runt-related transcription factor 2 (RUNX2), dentin matrix acidic phosphoprotein-1 (DMP1), and alkaline phosphatase...
December 19, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29249772/inhibition-of-adenosine-monophosphate-activated-protein-kinase-suppresses-bone-morphogenetic-protein-2-induced-mineralization-of-osteoblasts-via-smad-independent-mechanisms
#13
Ayumu Takeno, Ippei Kanazawa, Masakazu Notsu, Ken-Ichiro Tanaka, Toshitsugu Sugimoto
Previous studies showed that adenosine monophosphate-activated protein kinase (AMPK), which plays as an intracellular energy sensor, promotes the differentiation and mineralization of osteoblasts via enhancing expression of bone morphogenetic protein (BMP)-2, which is a potent inducer of osteoblastogenesis. Thus, the aim of this study was to examine the roles of AMPK in BMP-2-induced osteoblastogenesis. We used a murine osteoblastic cell line MC3T3-E1 and a murine marrow stromal cell line ST2. BMP-2 (50 and 100 ng/mL) stimulated alkaline phosphatase (ALP) activity and enhanced mineralization of MC3T3-E1 cells, while the effects of BMP-2 were partly abolished by an inhibitor of AMPK, ara-A (0...
December 16, 2017: Endocrine Journal
https://www.readbyqxmd.com/read/29234012/structural-basis-for-genome-wide-recognition-of-5-bp-gc-motifs-by-smad-transcription-factors
#14
Pau Martin-Malpartida, Marta Batet, Zuzanna Kaczmarska, Regina Freier, Tiago Gomes, Eric Aragón, Yilong Zou, Qiong Wang, Qiaoran Xi, Lidia Ruiz, Angela Vea, José A Márquez, Joan Massagué, Maria J Macias
Smad transcription factors activated by TGF-β or by BMP receptors form trimeric complexes with Smad4 to target specific genes for cell fate regulation. The CAGAC motif has been considered as the main binding element for Smad2/3/4, whereas Smad1/5/8 have been thought to preferentially bind GC-rich elements. However, chromatin immunoprecipitation analysis in embryonic stem cells showed extensive binding of Smad2/3/4 to GC-rich cis-regulatory elements. Here, we present the structural basis for specific binding of Smad3 and Smad4 to GC-rich motifs in the goosecoid promoter, a nodal-regulated differentiation gene...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29232368/ascorbic-acid-promotes-cardiomyogenesis-through-smad1-signaling-in-differentiating-mouse-embryonic-stem-cells
#15
Maria Grazia Perino, Satoshi Yamanaka, Daniel R Riordon, Yelena Tarasova, Kenneth R Boheler
Numerous groups have documented that Ascorbic Acid (AA) promotes cardiomyocyte differentiation from both mouse and human ESCs and iPSCs. AA is now considered indispensable for the routine production of hPSC-cardiomyocytes (CMs) using defined media; however, the mechanisms involved with the inductive process are poorly understood. Using a genetically modified mouse embryonic stem cell (mESC) line containing a dsRED transgene driven by the cardiac-restricted portion of the ncx1 promoter, we show that AA promoted differentiation of mESCs to CMs in a dose- and time-dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/29231215/involvement-of-fak-mediated-bmp-2-smad-pathway-in-mediating-osteoblast-adhesion-and-differentiation-on-nano-ha-chitosan-composite-coated-titanium-implant-under-diabetic-conditions
#16
Xiang-Yu Ma, Ya-Fei Feng, Tian-Sheng Wang, Wei Lei, Xiang Li, Da-Peng Zhou, Xin-Xin Wen, Hai-Long Yu, Liang-Bi Xiang, Lin Wang
Chitosan (CS)-based hydroxyapatite (HA) composites have emerged as a novel strategy for promoting bone regeneration. Here nanophase HA/CS composite coated porous titanium implants (nCT) were fabricated and their biological behavior under diabetic conditions was investigated. We proposed that the focal adhesion kinase (FAK)-mediated BMP-2/Smad pathway played a role in mediating the promotive effect of nCTs on osteoblast adhesion and differentiation under diabetes-induced high reactive oxygen species (ROS) condition...
December 12, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/29222456/bmps-as-new-insulin-sensitizers-enhanced-glucose-uptake-in-mature-3t3-l1-adipocytes-via-ppar%C3%AE-and-glut4-upregulation
#17
Isabelle Schreiber, Gina Dörpholz, Claus-Eric Ott, Bjørt Kragesteen, Nancy Schanze, Cory Thomas Lee, Josef Köhrle, Stefan Mundlos, Karen Ruschke, Petra Knaus
Insulin-resistance is the main cause of type 2 diabetes. Here we describe the identification and characterization of BMP2 and BMP6 as new insulin-sensitizing growth factors in mature adipocytes. We show that BMP2 and BMP6 lead to enhanced insulin-mediated glucose uptake in both insulin-sensitive and -insensitive adipocytes. We exclude a direct effect of BMP2 or BMP6 on translocation of GLUT4 to the plasma membrane and demonstrate that these BMPs increase GLUT4 protein levels equipotent to Rosiglitazone. BMPs induce expression of PPARγ as the crucial mediator for the insulin-sensitizing effect...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207198/mechanism-of-triptolide-in-treating-ankylosing-spondylitis-through-the-anti%C3%A2-ossification-effect-of-the-bmp-smad-signaling-pathway
#18
Guilong Wang, Jing Cai, Jinshan Zhang, Cuiyun Li
The present study aimed to examine the mechanism of triptolide in the treatment of ankylosing spondylitis (AS) through the anti‑ossification effect of bone morphogenetic protein (BMP)/small mothers against decapentaplegic (Smad) pathway. Male rats were randomly divided into five groups: Normal rat group; model group; triptolide low dose group (10 mg/kg); triptolide middle dose group (20 mg/kg); triptolide high dose group (40 mg/kg). The spinal joint capsules of each group of rats were collected to perform primary cell culture to determine the levels of cell proliferation...
November 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29202447/bone-forming-peptide-3-induces-osteogenic-differentiation-of-bone-marrow-stromal-cells-via-regulation-of-the-erk1-2-and-smad1-5-8-pathways
#19
Jun Sik Lee, Mi Eun Kim, Jong Keun Seon, Ju Yeon Kang, Taek Rim Yoon, Yong-Duk Park, Hyung Keun Kim
A bone-remodeling imbalance induced by increased bone resorption and osteoclast formation causes skeletal diseases such as osteoporosis. Induction of osteogenic differentiation of bone marrow stromal cells (BMSCs) leads to bone regeneration. Many researchers have tried to develop new adjuvants as specific stimulators of bone regeneration for therapeutic use in patients with bone resorption. We tried to develop a new adjuvant that has stronger osteogenic differentiation-promoting activity than bone morphogenetic proteins (BMPs)...
November 22, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29197384/involvement-of-the-bone-morphogenic-protein-smad-signaling-pathway-in-the-etiology-of-congenital-anomalies-of-the-kidney-and-urinary-tract-accompanied-by-cryptorchidism
#20
Kentaro Mizuno, Akihiro Nakane, Hidenori Nishio, Yoshinobu Moritoki, Hideyuki Kamisawa, Satoshi Kurokawa, Taiki Kato, Ryosuke Ando, Tetsuji Maruyama, Takahiro Yasui, Yutaro Hayashi
BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT), such as renal dysplasia, hydronephrosis, or vesicoureteral reflux, are the most common causes of end-stage renal disease. However, the genetic etiology of CAKUT remains unclear. In this study, we performed whole exome sequencing (WES) to elucidate the genetic etiology of symptomatic CAKUT and CAKUT accompanied by cryptorchidism. METHODS: Three patients with unilateral renal dysplasia accompanied by ipsilateral cryptorchidism were included in this analysis...
December 2, 2017: BMC Urology
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