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BMP signalling

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https://www.readbyqxmd.com/read/28102712/bone-morphogenetic-protein-2-and-7-mediate-the-anabolic-function-of-nucleus-pulposus-cells-with-discrete-mechanisms
#1
Victor Yl Leung, Lixiong Zhou, Wai-Kit Tam, Yi Sun, Fengjuan Lv, Guangqian Zhou, Kenneth Mc Cheung
Bone morphogenetic proteins (BMPs) play roles in promoting cell anabolism, especially extracellular matrix production. The difference between BMP members in their capacity to modulate intervertebral disc cell activity is yet to be defined. BMP-7/OP-1 has been shown to retard disc degeneration. We compared the activity of BMP-7 with BMP-2 on nucleus pulposus (NP) cell phenotype and function, and investigated how they differentially affect the gene expression profiles of signaling cascade components in human NP cells under degenerative states...
January 19, 2017: Connective Tissue Research
https://www.readbyqxmd.com/read/28100499/gremlin1-plays-a-key-role-in-kidney-development-and-renal-fibrosis
#2
Rachel H Church, Imran Ali, Mitchel Tate, Deborah Lavin, Arjun Krishnakumar, Helena M Kok, Roel Goldschmeding, Finian Martin, Derek Brazil
Grem1, an antagonist of bone morphogenetic proteins, plays a key role in embryogenesis. A highly specific temporospatial gradient of Grem1 and BMP signalling is critical to normal lung, kidney and limb development. Grem1 levels are increased in renal fibrotic conditions including acute kidney injury, diabetic nephropathy, chronic allograft nephropathy and immune glomerulonephritis. A small number of grem1-/- whole body knockout mice on a mixed genetic background (8 %) are viable, with a single, enlarged left kidney and grossly normal histology...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28094870/igf1r-signaling-acts-on-the-anagen-to-catagen-transition-in-the-hair-cycle
#3
Mathieu Castela, Fabien Linay, Edwige Roy, Philippe Moguelet, Jie Xu, Martin Holzenberger, Kiarash Khosrotehrani, Selim Aractingi
Insulin like growth factor 1 (IGF1) is important for skin development and homeostasis. However, overexpression and inactivation studies have produced variable findings regarding its role in hair follicle (HF) biology. Here, we studied a conditional and inducible knockout of the IGF1 receptor (IGF1R) in keratin 15-expressing bulge cells. Deletion of IGF1R after the development of the skin appendages in K15-IGF1R(KO) mice showed no abnormalities in epidermal homeostasis. Numbers of bulge cells were lower in K15-IGF1R(KO) mice than in controls, without consequences on wound healing, at least in young mice...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28076890/suppression-of-osteogenic-activity-by-regulation-of-wnt-and-bmp-signaling-during-titanium-particle-induced-osteolysis
#4
Ju-Suk Nam, Ashish Ranjan Sharma, Supriya Jagga, Dong-Hyun Lee, Garima Sharma, Lich Thi Nguyen, Yeon Hee Lee, Jun-Dong Chang, Chiranjib Chakraborty, Sang-Soo Lee
Periprosthetic osteolysis remains the leading obstacle for total joint replacements. Primarily, it was thought that aseptic loosening is mainly caused by macrophage mediated inflammatory process arising from production of wear debris. The role of osteoclasts and its sequential bone resorption ability has been extensively studied, but little is known about impaired osteogenesis during osteolysis. In the current study, we have tried to delineate the regulatory mechanism of osteogenic signals by Ti particles in osteoprogenitor cells as well its participatory role in wear debris induced osteolysis...
January 11, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28069701/loss-of-axin2-results-in-impaired-heart-valve-maturation-and-subsequent-myxomatous-valve-disease
#5
Alexia Hulin, Vicky Moore, Jeanne M James, Katherine E Yutzey
AIMS: Myxomatous valve disease (MVD) is the most common aetiology of primary mitral regurgitation. Recent studies suggest that defects in heart valve development can lead to heart valve disease in adults. Wnt/β-catenin signalling is active during heart valve development and has been reported in human MVD. The consequences of increased Wnt/β-catenin signalling due to Axin2 deficiency in postnatal valve remodelling and pathogenesis of MVD were determined. METHODS AND RESULTS: To investigate the role of Wnt/β-catenin signalling, we analysed heart valves from mice deficient in Axin2 (KO), a negative regulator of Wnt/β-catenin signalling...
January 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28068334/two-paralogous-tetraspanins-tsp-12-and-tsp-14-function-with-the-adam10-metalloprotease-sup-17-to-promote-bmp-signaling-in-caenorhabditis-elegans
#6
Lin Wang, Zhiyu Liu, Herong Shi, Jun Liu
The highly conserved bone morphogenetic protein (BMP) signaling pathway regulates many developmental and homeostatic processes. While the core components of the BMP pathway have been well studied, much research is needed for understanding the mechanisms involved in the precise spatiotemporal control of BMP signaling in vivo. Here, we provide evidence that two paralogous and evolutionarily conserved tetraspanins, TSP-12 and TSP-14, function redundantly to promote BMP signaling in C. elegans. We further show that the ADAM10 (a disintegrin and metalloprotease 10) ortholog SUP-17 also functions to promote BMP signaling, and that TSP-12 can bind to and promote the cell surface localization of SUP-17...
January 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28067796/combined-effects-of-androgen-and-growth-hormone-on-osteoblast-marker-expression-in-mouse-c2c12-and-mc3t3-e1-cells-induced-by-bone-morphogenetic-protein
#7
Kosuke Kimura, Tomohiro Terasaka, Nahoko Iwata, Takayuki Katsuyama, Motoshi Komatsubara, Ryota Nagao, Kenichi Inagaki, Fumio Otsuka
Osteoblasts undergo differentiation in response to various factors, including growth factors and steroids. Bone mass is diminished in androgen- and/or growth hormone (GH)-deficient patients. However the functional relationship between androgen and GH, and their combined effects on bone metabolism, remains unclear. Here we investigated the mutual effects of androgen and GH on osteoblastic marker expression using mouse myoblastic C2C12 and osteoblast-like MC3T3-E1 cells. Combined treatment with dihydrotestosterone (DHT) and GH enhanced BMP-2-induced expression of Runx2, ALP, and osteocalcin mRNA, compared with the individual treatments in C2C12 cells...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28064277/smad2-phosphorylation-in-diabetic-kidney-tubule-epithelial-cells-is-associated-with-modulation-of-several-transforming-growth-factor-%C3%AE-family-members
#8
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
BACKGROUND: The role of transforming growth factor-β (TGF-β) has recently gained much attention in diabetic nephropathy and kidney fibrosis. In this study, we extend this to an assessment of transcriptional regulation of the entire TGF-β superfamily in kidneys from diabetic vs. healthy mice. In order to study the translation between mouse model and patients, we evaluated the signature of phosphorylated Sma- and Mad-related protein 2 (pSmad2), as molecular marker of TGF-β/activin activity, in the kidneys of streptozotocin (STZ)-treated mice compared to that of type 1 diabetes (T1D) patients...
January 7, 2017: Nephron
https://www.readbyqxmd.com/read/28062564/tgf-%C3%AE-bone-morphogenetic-protein-and-activin-signaling-and-the-tumor-microenvironment
#9
Michael W Pickup, Philip Owens, Harold L Moses
The cellular and noncellular components surrounding the tumor cells influence many aspects of tumor progression. Transforming growth factor β (TGF-β), bone morphogenetic proteins (BMPs), and activins have been shown to regulate the phenotype and functions of the microenvironment and are attractive targets to attenuate protumorigenic microenvironmental changes. Given the pleiotropic nature of the cytokines involved, a full understanding of their effects on numerous cell types in many contexts is necessary for proper clinical intervention...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28062508/arterial-calcification-in-diabetes-mellitus-preclinical-models-and-translational-implications
#10
John N Stabley, Dwight A Towler
Diabetes mellitus increasingly afflicts our aging and dysmetabolic population. Type 2 diabetes mellitus and the antecedent metabolic syndrome represent the vast majority of the disease burden-increasingly prevalent in children and older adults. However, type 1 diabetes mellitus is also advancing in preadolescent children. As such, a crushing wave of cardiometabolic disease burden now faces our society. Arteriosclerotic calcification is increased in metabolic syndrome, type 2 diabetes mellitus, and type 1 diabetes mellitus-impairing conduit vessel compliance and function, thereby increasing the risk for dementia, stroke, heart attack, limb ischemia, renal insufficiency, and lower extremity amputation...
December 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28059714/regeneration-of-fat-cells-from-myofibroblasts-during-wound-healing
#11
Maksim V Plikus, Christian F Guerrero-Juarez, Mayumi Ito, Yun Rose Li, Priya H Dedhia, Ying Zheng, Mengle Shao, Denise L Gay, Raul Ramos, Tsai-Ching His, Ji Won Oh, Xiaojie Wang, Amanda Ramirez, Sara E Konopelski, Arijh Elzein, Anne Wang, Rarinthip June Supapannachart, Hye-Lim Lee, Chae Ho Lim, Arben Nace, Amy Guo, Elsa Treffeisen, Thomas Andl, Ricardo N Ramirez, Rabi Murad, Stefan Offermanns, Daniel Metzger, Pierre Chambon, Alan D Widgerow, Tai-Lan Tuan, Ali Mortazavi, Rana K Gupta, Bruce A Hamilton, Sarah E Millar, Patrick Seale, Warren S Pear, Mitchell A Lazar, George Cotsarelis
Although regeneration via the reprogramming of one cell lineage to another occurs in fish and amphibians, it is not observed in mammals. We discovered in mouse that during wound healing adipocytes regenerate from myofibroblasts, a cell type thought to be differentiated and non-adipogenic. Myofibroblast reprogramming required neogenic hair follicles, which triggered BMP signaling and then activation of adipocyte transcription factors expressed during development. Overexpression of the BMP antagonist, noggin, in hair follicles or deletion of the BMP receptor in myofibroblasts prevented adipocyte formation...
January 5, 2017: Science
https://www.readbyqxmd.com/read/28059064/bmp-restricts-stemness-of-intestinal-lgr5-stem-cells-by-directly-suppressing-their-signature-genes
#12
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/28052263/amplification-of-adipogenic-commitment-by-vstm2a
#13
Blandine Secco, Étienne Camiré, Marc-Antoine Brière, Alexandre Caron, Armande Billong, Yves Gélinas, Anne-Marie Lemay, Kevin M Tharp, Peter L Lee, Stéphane Gobeil, Jean V Guimond, Natacha Patey, David A Guertin, Andreas Stahl, Élie Haddad, David Marsolais, Yohan Bossé, Kivanc Birsoy, Mathieu Laplante
Despite progress in our comprehension of the mechanisms regulating adipose tissue development, the nature of the factors that functionally characterize adipose precursors is still elusive. Defining the early steps regulating adipocyte development is needed for the generation of tools to control adipose tissue size and function. Here, we report the discovery of V-set and transmembrane domain containing 2A (VSTM2A) as a protein expressed and secreted by committed preadipocytes. VSTM2A expression is elevated in the early phases of adipogenesis in vitro and adipose tissue development in vivo...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28052036/angiomotin-regulates-prostate-cancer-cell-proliferation-by-signaling-through-the-hippo-yap-pathway
#14
Hao Zeng, Angelica Ortiz, Peng-Fei Shen, Chien-Jui Cheng, Yu-Chen Lee, Guoyu Yu, Song-Chang Lin, Chad J Creighton, Li-Yuan Yu-Lee, Sue-Hwa Lin
Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3, DU145, and BPH1 cells...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051358/controlled-retention-of-bmp-2-derived-peptide-on-nanofibers-based-on-mussel-inspired-adhesion-for-bone-formation
#15
Jinkyu Lee, Sajeesh Kumar Mp, Taufiq Ahmad, Min Suk Lee, Heeseok Yang, Do-Gyoon Kim, Kyobum Kim, Bosun Kwon, Heungsoo Shin
Although bone morphogenetic protein-2 (BMP-2) has been frequently used to stimulate bone formation, it has several side effects to be addressed, including the difficulty in optimization of clinically relevant doses and unwanted induction of cancerous signaling processes. In this study, an osteogenic peptide (OP) derived from BMP-2 was investigated as a substitute for BMP-2. In vitro studies showed that OP was able to enhance in the osteogenic differentiation and mineralization of human mesenchymal stem cells (hMSCs)...
January 4, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28045533/computational-model-of-secondary-palate-fusion-and-disruption
#16
M Shane Hutson, Maxwell C K Leung, Nancy Baker, Richard M Spencer, Thomas B Knudsen
Morphogenetic events are driven by cell-generated physical forces and complex cellular dynamics. To improve our capacity to predict developmental effects from chemical-induced cellular alterations, we built a multi-cellular agent-based model in CompuCell3D that recapitulates the cellular networks and collective cell behavior underlying growth and fusion of the mammalian secondary palate. The model incorporated multiple signaling pathways (TGFβ, BMP, FGF, EGF, SHH) in a biological framework to recapitulate morphogenetic events from palatal outgrowth through midline fusion...
January 3, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28045022/jak-stat-controls-organ-size-and-fate-specification-by-regulating-morphogen-production-and-signalling
#17
Carles Recasens-Alvarez, Ana Ferreira, Marco Milán
A stable pool of morphogen-producing cells is critical for the development of any organ or tissue. Here we present evidence that JAK/STAT signalling in the Drosophila wing promotes the cycling and survival of Hedgehog-producing cells, thereby allowing the stable localization of the nearby BMP/Dpp-organizing centre in the developing wing appendage. We identify the inhibitor of apoptosis dIAP1 and Cyclin A as two critical genes regulated by JAK/STAT and contributing to the growth of the Hedgehog-expressing cell population...
January 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28043948/angptl2-expression-in-the-intestinal-stem-cell-niche-controls-epithelial-regeneration-and-homeostasis
#18
Haruki Horiguchi, Motoyoshi Endo, Kohki Kawane, Tsuyoshi Kadomatsu, Kazutoyo Terada, Jun Morinaga, Kimi Araki, Keishi Miyata, Yuichi Oike
The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Dysregulation of intestinal epithelial homeostasis leads to severe inflammatory bowel disease. Additionally, aberrant signaling by the secreted protein angiopoietin-like protein 2 (ANGPTL2) causes chronic inflammation in a variety of diseases. However, little is known about the physiologic role of ANGPTL2 in normal tissue homeostasis and during wound repair following injury. Here, we assessed ANGPTL2 function in intestinal physiology and disease in vivo Although intestinal development proceeded normally in Angptl2-deficient mice, expression levels of the intestinal stem cell (ISC) marker gene Lgr5 decreased, which was associated with decreased transcriptional activity of β-catenin in Angptl2-deficient mice...
January 2, 2017: EMBO Journal
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
#19
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/28039430/inflammation-and-vascular-smooth-muscle-cell-dedifferentiation-following-carotid-artery-ligation
#20
Brian Paul Herring, April M Hoggatt, Sarah L Griffith, Jeanette N McClintick, Patricia Jane Gallagher
OBJECTIVE: Following vascular injury medial smooth muscle cells dedifferentiate and migrate through the internal elastic lamina where they form a neointima. The goal of the current study was to identify changes in gene expression that occur prior to the development of neointima and are associated with the early response to injury. Approach and Results: Vascular injury was induced in C57Bl/6 mice and in Myh11-creER(T2) mTmG reporter mice by complete ligation of the left carotid artery...
December 30, 2016: Physiological Genomics
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