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BMP AND smad

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https://www.readbyqxmd.com/read/28202676/harnessing-the-bmp-signaling-pathway-to-control-the-formation-of-cancer-stem-cells-by-effects-on-epithelial-to-mesenchymal-transition
#1
REVIEW
Ashish Bosukonda, William D Carlson
Cancer stem cells (CSCs) persist in tumors as a distinct population and may be causative in metastasis and relapse. CSC-rich tumors are associated with higher rates of metastasis and poor patient prognosis. Targeting CSCs therapeutically is challenging, since they seem to be resistant to standard chemotherapy. We have shown that a novel peptide agonist of bone morphogenetic protein (BMP) signaling, P123, is capable of inhibiting the growth of primary tumor cells by interacting with type I receptors selectively [activin receptor-like kinase 2 (ALK2) and ALK3, but not ALK6] and type II BMP receptors, activating SMAD 1/5/8 signaling and controlling the cell cycle pathway...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28188849/endocytosis-contributes-to-bmp2-induced-smad-signalling-and-neuronal-growth
#2
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...
February 7, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28182872/enhanced-critical-size-calvarial-bone-healing-by-ascs-engineered-with-cre-loxp-based-hybrid-baculovirus
#3
Shih-Chun Lo, Kuei-Chang Li, Yu-Han Chang, Mu-Nung Hsu, Li-Yu Sung, Truong Anh Vu, Yu-Chen Hu
Calvarial bone repair remains challenging for adults. Although adipose-derived stem cells (ASCs) hold promise to heal bone defects, use of ASCs for critical-size calvarial bone repair is ineffective. Stromal cell-derived factor 1 (SDF-1) is a chemokine capable of triggering stem cell migration. Although recombinant SDF-1 protein is co-delivered with other molecules including BMP-2 to facilitate calvarial bone repair, these approaches did not yield satisfactory healing. This study aimed to exploit a newly developed Cre/loxP-based hybrid baculovirus for efficient gene delivery and prolonged transgene expression in ASCs...
January 30, 2017: Biomaterials
https://www.readbyqxmd.com/read/28155178/tumor-necrosis-factor-%C3%AE-and-transforming-growth-factor-%C3%AE-1-facilitate-differentiation-and-proliferation-of-tendon-derived-stem-cells-in-vitro
#4
Peilin Han, Qingbo Cui, Shulong Yang, Hao Wang, Peng Gao, Zhaozhu Li
OBJECTIVES: To investigate the effects of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) on the proliferation and differentiation of tendon-derived stem cells (TDSC). RESULTS: TNF-α inhibits the proliferation and tenogenic/osteogenic differentiation of TDSC but, after simultaneous or sequential treatment with TGF-β1 and TNF-α, the expression of tenogenic/osteogenic-related marker and proliferation of TDSC was significantly increased...
February 2, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28152139/bone-morphogenetic-protein-7-suppresses-tgf%C3%AE-2-induced-epithelial-mesenchymal-transition-in-the-lens-implications-for-cataract-prevention
#5
Daisy Y Shu, Magdalena C Wojciechowski, Frank J Lovicu
Purpose: Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a key pathologic mechanism underlying cataract. Two members of the transforming growth factor-β (TGFβ) superfamily, TGFβ and bone morphogenetic protein-7 (BMP-7) have functionally distinct roles in EMT. While TGFβ is a potent inducer of EMT, BMP-7 counteracts the fibrogenic activity of TGFβ. We examine the modulating effect of BMP-7 on TGFβ-induced EMT in LECs. Methods: Rat lens epithelial explants were treated exogenously with TGFβ2 alone or in combination with BMP-7 for up to 5 days...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28134270/signal-mingle-micropatterns-of-bmp-2-and-fibronectin-on-soft-biopolymeric-films-regulate-myoblast-shape-and-smad-signaling
#6
Vincent Fitzpatrick, Laure Fourel, Olivier Destaing, Flora Gilde, Corinne Albigès-Rizo, Catherine Picart, Thomas Boudou
In vivo, bone morphogenetic protein 2 (BMP-2) exists both in solution and bound to the extracellular matrix (ECM). While these two modes of presentation are known to influence cell behavior distinctly, their role in the niche microenvironment and their functional relevance in the genesis of a biological response has sparsely been investigated at a cellular level. Here we used the natural affinity of BMP-2 for fibronectin (FN) to engineer cell-sized micropatterns of BMP-2. This technique allowed the simultaneous control of the spatial presentation of fibronectin-bound BMP-2 and cell spreading...
January 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28128304/targeting-osteoblastic-casein-kinase-2-interacting-protein-1-to-enhance-smad-dependent-bmp-signaling-and-reverse-bone-formation-reduction-in-glucocorticoid-induced-osteoporosis
#7
Jin Liu, Changwei Lu, Xiaohao Wu, Zongkang Zhang, Jie Li, Baosheng Guo, Defang Li, Chao Liang, Lei Dang, Xiaohua Pan, Songlin Peng, Aiping Lu, Baoting Zhang, Ge Zhang
The underlying mechanism of the reduced bone formation during the development of glucocorticoid-induced osteoporosis (GIO) remains unclear. Here, we found that the highly expressed CKIP-1 together with lowly expressed total and phosphorylated Smad1/5 in bone samples was accompanied by either the reduced serum bone formation markers in GIO patients or the decreased bone formation in GIO mice. In vitro studies showed that the highly expressed CKIP-1 could promote Smad1 ubiquitination to suppress the Smad-dependent BMP signaling and inhibit osteogenic differentiation and mineral deposition in MC3T3-E1 cells during glucocorticoid treatment...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28126904/biochemical-and-cellular-analysis-reveals-ligand-binding-specificities-a-molecular-basis-for-ligand-recognition-and-membrane-association-dependent-activities-of-cripto-1-and-cryptic
#8
Senem Aykul, Anthony Parenti, Kit Yee Chu, Jake Reske, Monique Floer, Amy Ralston, Erik Martinez-Hackert
Transforming growth factor beta (TGF-β) pathways are key determinants of cell fate in animals. Their basic mechanism of action is simple. However, to produce cell-specific responses, TGF-β pathways are heavily regulated by secondary factors, such as membrane-associated EGF-CFC family proteins. Cellular activities of EGF-CFC proteins have been described, but their molecular functions, including how the mammalian homologs Cripto-1 and Cryptic recognize and regulate TGF-β family ligands, are less clear. Here we use purified human Cripto-1 and mouse Cryptic produced in mammalian cells to show that these two EGF-CFC homologs have distinct, highly specific ligand binding activities...
January 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28124060/bone-morphogenetic-protein-4-regulates-micrornas-mir-494-and-mir-126-5p-in-control-of-endothelial-cell-function-in-angiogenesis
#9
Jennifer S Esser, Erika Saretzki, Franziska Pankratz, Bianca Engert, Sebastian Grundmann, Christoph Bode, Martin Moser, Qian Zhou
MicroRNAs are small non-coding RNAs that negatively regulate posttranscriptional gene expression. Several microRNAs have been described to regulate the process of angiogenesis. Previously, we have shown that bone morphogenetic protein 4 (BMP4) increased the pro-angiogenic activity of endothelial cells. In this project, we now investigated how the pro-angiogenic BMP4 effect is mediated by microRNAs. First, we performed a microRNA array with BMP4-stimulated human umbilical vein endothelial cells (HUVECs). Among the top-regulated microRNAs, we detected a decreased expression of miR-494 and increased expression of miR-126-5p...
January 26, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28059064/bmp-restricts-stemness-of-intestinal-lgr5-stem-cells-by-directly-suppressing-their-signature-genes
#10
Zhen Qi, Yehua Li, Bing Zhao, Chi Xu, Yuan Liu, Haonan Li, Bingjie Zhang, Xinquan Wang, Xiao Yang, Wei Xie, Baojie Li, Jing-Dong Jackie Han, Ye-Guang Chen
The intestinal epithelium possesses a remarkable self-renewal ability, which is mediated by actively proliferating Lgr5(+) stem cells. Bone morphogenetic protein (BMP) signalling represents one major counterforce that limits the hyperproliferation of intestinal epithelium, but the exact mechanism remains elusive. Here we demonstrate that epithelial BMP signalling plays an indispensable role in restricting Lgr5(+) stem cell expansion to maintain intestinal homeostasis and prevent premalignant hyperproliferation on damage...
January 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28040510/du-huo-ji-sheng-tang-and-its-active-component-ligusticum-chuanxiong-promote-osteogenic-differentiation-and-decrease-the-aging-process-of-human-mesenchymal-stem-cells
#11
Jir-You Wang, Che-Sheng Wen, Shih-Chieh Hung, Pei-Wen Chen, Jen-Hwey Chiu
ETHNOPHARMACOLOGICAL RELEVANCE: Postmenopausal osteoporosis is the most common bone disease worldwide. Information concerning the effects of herbal medicines on mesenchymal cell osteogenesis and senescence remains lacking. AIM OF THIS STUDY: This study was designed to investigate the effects of Du-Huo-Ji-Sheng-Tang (DHJST), a Chinese herbal medicine and its active component Ligusticum chuanxiong on osteogenic differentiation and the aging process of human mesenchymal cells (hMSCs)...
December 28, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28030800/the-role-of-mir-17-92-in-the-miregulatory-landscape-of-ewing-sarcoma
#12
Raphaela Schwentner, David Herrero-Martin, Maximilian O Kauer, Cornelia N Mutz, Anna M Katschnig, Grzegorz Sienski, Javier Alonso, Dave Nt Aryee, Heinrich Kovar
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3'UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing sarcoma. MiR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be among the top EWS-FLI1 activated miRNAs...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28029182/nedd4-deficiency-in-vascular-smooth-muscle-promotes-vascular-calcification-by-stabilizing-psmad1
#13
Ji-Hyun Lee, Seon-Ae Jeon, Byung-Gyu Kim, Michiko Takeda, Jae-Jin Cho, Dong-Ik Kim, Hiroshi Kawabe, Je-Yoel Cho
The nonosseous calcification process such as atherosclerosis is one of the major complications in several types of metabolic diseases. In previous study, we uncovered that aberrant activity of TGF-β signaling pathway could contribute the vascular smooth muscle cells (VSMCs) calcification process. Also, we identified NEDD4 E3 ligase as a key suppressor of BMP/Smad pathway via a polyubiquitination dependent selective degradation of C-terminal phosphorylated Smad1 (pSmad1) activated by TGF-β⋅ Here, we further validated and confirmed the role of Nedd4 in in vivo vascular calcification progression...
December 28, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27996168/follicle-stimulating-hormone-%C3%AE-subunit-potentiates-bone-morphogenetic-protein-9-induced-osteogenic-differentiation-in-mouse-embryonic-fibroblasts
#14
Xiao-Ya Su, Xiang Zou, Qian-Zhao Chen, Yu-Hua Zeng, Ying Shao, Bai-Cheng He, Hong Liu
Postmenopausal osteoporosis (PMOP)-related fractures usually result in morbidity and mortality in aging women, so it is remains a global public health concern, and new effective safe treatments are urgently needed recently. Efficient osteogenesis from mesenchymal stem cells (MSCs) would have the clinical application potential in treating multiple osteal disorders. Follicle-stimulating hormone (FSH), a pituitary glycoprotein hormone highly associated with menopausal bone turnover, whose peculiar part of receptor binding is follicle-stimulating hormone β-subunit (FSHβ)...
December 20, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27995357/bone-morphogenetic-protein-modulator-bmper-regulates-endothelial-barrier-function
#15
Thomas Helbing, Gwendoline Wiltgen, Alexandra Hornstein, Elena Z Brauers, Linus Arnold, Adrian Bauer, Jennifer S Esser, Philipp Diehl, Sebastian Grundmann, Katrin Fink, Cam Patterson, Christoph Bode, Martin Moser
The endothelium serves as a selective barrier and controls the exchange of nutrients, hormones, and leukocytes between blood and tissues. Molecular mechanisms contributing to the pathogenesis of endothelial barrier dysfunction remain incompletely understood. Accumulating evidence implicates bone morphogenetic protein (BMP)-modulator BMPER as a key regulator in endothelial biology. Herein, we analyze the impact of BMPER in the control of endothelial barrier function. To assess the role of BMPER in vascular barrier function in mice, we measured the leakage of Evans blue dye from blood into interstitial lung tissue...
December 19, 2016: Inflammation
https://www.readbyqxmd.com/read/27986931/bone-morphogenetic-protein-2-regulates-cell-cell-communication-by-down-regulating-connexin43-expression-in-luteinized-human-granulosa-cells
#16
Yan-Ting Wu, Hsun-Ming Chang, He-Feng Huang, Jian-Zhong Sheng, Peter C K Leung
STUDY QUESTION: Does bone morphogenetic protein 2 (BMP2) regulate connexin43 (Cx43) and modulate cell-cell communication in luteinized human granulosa cells? SUMMARY ANSWER: BMP2 decreases gap junction intercellular communication (GJIC) of luteinized human granulosa cells by down-regulating Cx43 expression through an activin receptor-like kinase (ALK)2/ALK3-mediated Sma- and Mad-related protein (SMAD)-dependent signaling pathway. WHAT IS KNOWN ALREADY: BMP2 and its putative receptors are highly expressed in the human corpus luteum and are involved in the process of luteolysis...
December 16, 2016: Molecular Human Reproduction
https://www.readbyqxmd.com/read/27979781/the-binding-of-the-bone-morphogenetic-protein-antagonist-gremlin-to-kidney-heparan-sulfate-such-binding-is-not-essential-for-bmp-antagonism
#17
Arnold Junior Tatsinkam, Naomi Rune, Joy Smith, Jill T Norman, Barbara Mulloy, Christopher C Rider
Gremlin-1, a bone morphogenetic protein (BMP) antagonist, has essential roles in kidney and limb bone development, and is important in chronic diseases including tissue fibrosis. It also functions as an activating ligand of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), and binds strongly to the sulfated polysaccharide, heparin. Here we investigated the extent to which gremlin binds to the related polysaccharide heparan sulfate (HS), which unlike heparin is widely distributed spread within tissues...
December 12, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27941807/self-organized-amniogenesis-by-human-pluripotent-stem-cells-in-a-biomimetic-implantation-like-niche
#18
Yue Shao, Kenichiro Taniguchi, Katherine Gurdziel, Ryan F Townshend, Xufeng Xue, Koh Meng Aw Yong, Jianming Sang, Jason R Spence, Deborah L Gumucio, Jianping Fu
Amniogenesis-the development of amnion-is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment...
December 12, 2016: Nature Materials
https://www.readbyqxmd.com/read/27932702/incorporation-of-cerium-oxide-into-hydroxyapatite-coating-regulates-osteogenic-activity-of-mesenchymal-stem-cell-and-macrophage-polarization
#19
Kai Li, Qingyi Shen, Youtao Xie, Mingyu You, Liping Huang, Xuebin Zheng
Biomedical coatings for orthopedic implants should facilitate osseointegration and mitigate implant-induced inflammatory reactions. Cerium oxide (CeO2) ceramics possess anti-oxidative properties and can be used to decrease mediators of inflammation, which makes them attractive for biomedical applications. In our work, two kinds of CeO2 incorporated hydroxyapatite coatings (HA-10Ce and HA-30Ce) were prepared via plasma spraying technique and the effects of CeO2 addition on the responses of bone mesenchymal stem cells (BMSCs) and RAW264...
February 2017: Journal of Biomaterials Applications
https://www.readbyqxmd.com/read/27922109/regulation-of-hepcidin-expression-by-inflammation-induced-activin-b
#20
Yohei Kanamori, Makoto Sugiyama, Osamu Hashimoto, Masaru Murakami, Tohru Matsui, Masayuki Funaba
Activin B is induced in response to inflammation in the liver and enhances hepcidin expression, but the source of activin B and the molecular mechanism underlying hepcidin induction are not clear yet. Lipopolysaccharide (LPS)-induced inflammation induced inhibin βB but not inhibin α or inhibin βA expression in the liver, implicating activin B induction. Immunoreactive inhibin βB was detected in endothelial cells and Kupffer cells in LPS-treated liver. Activin B, but not activin A or activin AB, directly increased hepcidin expression...
December 6, 2016: Scientific Reports
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