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BMP AND smad

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https://www.readbyqxmd.com/read/28542453/extracellular-calcium-promotes-bone-formation-from-bone-marrow-mesenchymal-stem-cells-by-amplifying-the-effects-of-bmp-2-on-smad-signalling
#1
Rubén Aquino-Martínez, Natalia Artigas, Beatriz Gámez, José Luis Rosa, Francesc Ventura
Understanding the molecular events that regulate osteoblast differentiation is essential for the development of effective approaches to bone regeneration. In this study, we analysed the osteoinductive properties of extracellular calcium in bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation. We cultured BM-MSCs in 3D gelatin scaffolds with Ca2+ and BMP-2 as osteoinductive agents. Early and late osteogenic gene expression and bone regeneration in a calvarial critical-size defect model demonstrate that extracellular Ca2+ enhances the effects of BMP-2 on Osteocalcin, Runx2 and Osterix expression and promotes bone regeneration in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28494020/pannexin-3-regulates-proliferation-and-differentiation-of-odontoblasts-via-its-hemichannel-activities
#2
Tsutomu Iwamoto, Takashi Nakamura, Masaki Ishikawa, Keigo Yoshizaki, Asuna Sugimoto, Hiroko Ida-Yonemochi, Hayato Ohshima, Masahiro Saito, Yoshihiko Yamada, Satoshi Fukumoto
Highly coordinated regulation of cell proliferation and differentiation contributes to the formation of functionally shaped and sized teeth; however, the mechanism underlying the switch from cell cycle exit to cell differentiation during odontogenesis is poorly understood. Recently, we identified pannexin 3 (Panx3) as a member of the pannexin gap junction protein family from tooth germs. The expression of Panx3 was predominately localized in preodontoblasts that arise from dental papilla cells and can differentiate into dentin-secreting odontoblasts...
2017: PloS One
https://www.readbyqxmd.com/read/28489849/utilizing-bmp-2-muteins-for-treatment-of-multiple-myeloma
#3
Axel Seher, Charlotte Lagler, Thorsten Stühmer, Urs Dietmar Achim Müller-Richter, Alexander Christian Kübler, Walter Sebald, Thomas Dieter Müller, Joachim Nickel
Multiple myeloma (MM) represents a haematological cancer characterized by the pathological hyper proliferation of antibody-producing B-lymphocytes. Patients typically suffer from kidney malfunction and skeletal disorders. In the context of MM, the transforming growth factor β (TGFβ) member Activin A was recently identified as a promoter of both accompanying symptoms. Because studies have shown that bone morphogenetic protein (BMP)-2-mediated activities are counteracted by Activin A, we analysed whether BMP2, which also binds to the Activin A receptors ActRII and ActRIIB but activates the alternative SMAD-1/5/8 pathway, can be used to antagonize Activin A activities, such as in the context of MM...
2017: PloS One
https://www.readbyqxmd.com/read/28489579/transforming-growth-factor-%C3%AE-a-potential-biomarker-and-therapeutic-target-of-ventricular-remodeling
#4
REVIEW
Yuan Ma, Hai Zou, Xing-Xing Zhu, Jie Pang, Qiang Xu, Qin-Yang Jin, Ya-Hui Ding, Bing Zhou, Dong-Sheng Huang
Transforming growth factor β (TGF-β) is a multifunctional cytokine that is synthesized by many types of cells and regulates the cell cycle. Increasing evidence has led to TGF-β receiving increased and deserved attention in recent years because it may play a potentially novel and critical role in the development and progression of myocardial fibrosis and the subsequent progress of ventricular remodeling (VR). Numerous studies have highlighted a crucial role of TGF-β in VR and suggest potential therapeutic targets of the TGF-β signaling pathways for VR...
April 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28476867/regulatory-mechanisms-of-metamorphic-neuronal-remodeling-revealed-through-a-genome-wide-modifier-screen-in-drosophila-melanogaster
#5
Dahong Chen, Tingting Gu, Tom N Pham, Montgomery J Zachary, Randall S Hewes
During development, neuronal remodeling shapes neuronal connections to establish fully mature and functional nervous systems. Our previous studies have shown that the RNA binding factor alan shepard (shep) is an important regulator of neuronal remodeling during metamorphosis in Drosophila melanogaster, and loss of shep leads to smaller soma size and fewer neurites in a stage-dependent manner. To shed light on the mechanisms by which shep regulates neuronal remodeling, we conducted a genetic modifier screen for suppressors of shep-dependent wing expansion defects and cellular morphological defects in a set of peptidergic neurons, the bursicon neurons, that promote post-eclosion wing expansion...
May 5, 2017: Genetics
https://www.readbyqxmd.com/read/28469774/effects-of-altered-cxcl12-cxcr4-axis-on-bmp2-smad-runx2-osterix-axis-and-osteogenic-gene-expressions-during-osteogenic-differentiation-of-mscs
#6
Zhanghua Li, Wei Wang, Haijia Xu, Yu Ning, Weijun Fang, Wen Liao, Ji Zou, Yi Yang, Ningsheng Shao
This study investigated the effects of altered CXCL12/CXCR4 axis on the bone morphogenetic protein 2 (BMP-2)/Smad/runt-related transcription factor 2 (Runx2)/Osterix (Osx) signal axis and osteogenic gene expression during osteogenic differentiation of mesenchymal stem cells (MSCs), to gain understanding of the link between migration and osteogenic differentiation signal axis and MSCs osteogenic differentiation mechanisms. The pHBAd-MCMV- CXCL12-GFP vector (Ad-CXCL12) was constructed and quantitative polymerase chain reaction (qPCR)/western blotting used to determine CXCL12 expression in Ad-CXCL12-transfected MSCs...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28468752/usp4-inhibits-smad4-monoubiquitination-and-promotes-activin-and-bmp-signaling
#7
Fangfang Zhou, Feng Xie, Ke Jin, Zhengkui Zhang, Marcello Clerici, Rui Gao, Maarten van Dinther, Titia K Sixma, Huizhe Huang, Long Zhang, Peter Ten Dijke
SMAD4 is a common intracellular effector for TGF-β family cytokines, but the mechanism by which its activity is dynamically regulated is unclear. We demonstrated that ubiquitin-specific protease (USP) 4 strongly induces activin/BMP signaling by removing the inhibitory monoubiquitination from SMAD4. This modification was triggered by the recruitment of the E3 ligase, SMURF2, to SMAD4 following ligand-induced regulatory (R)-SMAD-SMAD4 complex formation. Whereas the interaction of the negative regulator c-SKI inhibits SMAD4 monoubiquitination, the ligand stimulates the recruitment of SMURF2 to the c-SKI-SMAD2 complex and triggers c-SKI ubiquitination and degradation...
May 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28467498/spatial-regulation-of-bone-morphogenetic-proteins-bmps-in-postnatal-articular-and-growth-plate-cartilage
#8
Presley Garrison, Shanna Yue, Jeffrey Hanson, Jeffrey Baron, Julian C Lui
Articular and growth plate cartilage both arise from condensations of mesenchymal cells, but ultimately develop important histological and functional differences. Each is composed of three layers-the superficial, mid and deep zones of articular cartilage and the resting, proliferative and hypertrophic zones of growth plate cartilage. The bone morphogenetic protein (BMP) system plays an important role in cartilage development. A gradient in expression of BMP-related genes has been observed across growth plate cartilage, likely playing a role in zonal differentiation...
2017: PloS One
https://www.readbyqxmd.com/read/28465413/bmp8a-sustains-spermatogenesis-by-activating-both-smad1-5-8-and-smad2-3-in-spermatogonia
#9
Fang-Ju Wu, Ting-Yu Lin, Li-Ying Sung, Wei-Fang Chang, Po-Chih Wu, Ching-Wei Luo
Mutation in either of the genes encoding bone morphogenetic protein (BMP) 8A or 8B (Bmp8a or Bmp8b) causes postnatal depletion of spermatogonia in mice. We found that Bmp8a, but not Bmp8b, was expressed predominantly in the neonatal mouse spermatogonia. Although most BMPs induce activation of SMADs 1, 5, and 8 (SMAD1/5/8), but not SMADs 2 and 3 (SMAD2/3), we found that BMP8A induced signaling through both sets of transcription factors. In undifferentiated mouse spermatogonia, BMP8A activated SMAD1/5/8 through receptor complexes formed by ALK3 and either ACVR2A or BMPR2 and activated SMAD2/3 through receptor complexes formed by ALK5 and ACVR2A, ACVR2B, or TGFBR2...
May 2, 2017: Science Signaling
https://www.readbyqxmd.com/read/28464239/combined-effects-of-bone-morphogenetic-protein-10-and-crossveinless-2-on-cardiomyocyte-differentiation-in-mouse-adipocyte-derived-stem-cells
#10
Medet Jumabay, Jiayinaguli Zhumabai, Nurlan Mansurov, Katharine C Niklason, Pierre J Guihard, Alan M Fogelman, Luisa Iruela-Arispe, Yucheng Yao, Arman Saparov, Kristina I Boström
Bone morphogenetic protein (BMP) 10, a cardiac-restricted BMP family member, is essential in cardiomyogenesis, especially during trabeculation. Crossveinless-2 [CV2, also known as BMP endothelial cell precursor derived regulator (BMPER)] is a BMP-binding protein that modulates the activity of several BMPs. The objective of this study was to examine the combined effects of BMP10 and CV2 on cardiomyocyte differentiation using mouse dedifferentiated fat (mDFAT) cells, which spontaneously differentiate into cardiomyocyte-like cells, as a model...
May 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28438754/smad1-5-is-required-for-erythropoietin-mediated-suppression-of-hepcidin-in-mice
#11
Chia-Yu Wang, Amanda B Core, Susanna Canali, Kimberly B Zumbrennen-Bullough, Sinan Ozer, Lieve Umans, An Zwijsen, Jodie L Babitt
Anemia suppresses liver hepcidin expression to supply adequate iron for erythropoiesis. Erythroferrone mediates hepcidin suppression by anemia, but its mechanism of action remains uncertain. The bone morphogenetic protein (BMP)-SMAD signaling pathway has a central role in hepcidin transcriptional regulation. Here, we explored the contribution of individual receptor-activated SMADs in hepcidin regulation and their involvement in erythroferrone suppression of hepcidin. In Hep3B cells, SMAD5 or SMAD1, but not SMAD8, knockdown inhibited hepcidin (HAMP) mRNA expression...
April 24, 2017: Blood
https://www.readbyqxmd.com/read/28426320/transient-exposure-to-androgens-induces-a-remarkable-self-sustained-quiescent-state-in-dispersed-prostate-cancer-cells
#12
Anh Thu Bui, Meng-Er Huang, Maryline Havard, Fanny Laurent-Tchenio, François Dautry, Thierry Tchenio
Cellular quiescence is a reversible cell growth arrest that is often assumed to require a persistence of non-permissive external growth conditions for its maintenance. In this work, we showed that androgen could induce a quiescent state that is self-sustained in a cell-autonomous manner through a "hit and run" mechanism in androgen receptor-expressing prostate cancer cells. This phenomenon required the set-up of a sustained redox imbalance and TGFβ/BMP signaling that were dependent on culturing cells at low density...
May 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28424263/the-kielin-chordin-like-protein-kcp-attenuates-high-fat-diet-induced-obesity-and-metabolic-syndrome-in-mice
#13
Abdul Soofi, Katherine I Wolf, Margo P Emont, Nathan Qi, Gabriel Martinez-Santibanez, Edward Grimley, Wesam Ostwani, Gregory R Dressler
Obesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions. In mice, the TGF-beta superfamily is implicated in the regulation of white and brown adipose tissue differentiation. The Kielin/chordin-like Protein (KCP) is a secreted regulator of the TGF-beta superfamily pathways that can inhibit both TGF-beta and activin signals while enhancing bone morphogenetic protein (BMP) signaling. However, KCP's effects on metabolism and obesity have not been studied in animal models...
April 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28391780/clinical-significance-linked-to-functional-defects-in-bone-morphogenetic-protein-type-2-receptor-bmpr2
#14
Myung-Jin Kim, Seon Young Park, Hae Ryung Chang, Eun Young Jung, Anudari Munkhjargal, Jong-Seok Lim, Myeong-Sok Lee, Yonghwan Kim
Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth factor-β (TGF-β) superfamily receptors, playing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD family of proteins-mediated signal transduction leading to expression of target genes implicated in development or differentiation of the embryo, organs and bones...
April 10, 2017: BMB Reports
https://www.readbyqxmd.com/read/28377507/an-epigenetic-regulatory-loop-controls-pro-osteogenic-activation-by-tgf-%C3%AE-1-or-bone-morphogenetic-protein-2-in-human-aortic-valve-interstitial-cells
#15
Rui Song, David A Fullerton, Lihua Ao, Ke-Seng Zhao, Xianzhong Meng
Calcific aortic valve disease (CAVD) is common in the elderly population, but pharmacological interventions for managing valvular calcification are unavailable. Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2) induce pro-osteogenic activation of human aortic valve interstitial cells (AVICs) that play an important role in valvular calcification. However, the molecular mechanism underlying pro-osteogenic activation in AVICs is incompletely understood. Here, we investigated an epigenetic regulatory mechanism in human AVIC pro-osteogenic activation induced by TGF-β1 and BMP-2...
April 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28356442/modulation-of-endothelial-bmpr2-activity-by-vegfr3-in-pulmonary-arterial-hypertension
#16
Cheol Hwangbo, Heon-Woo Lee, Hyeseon Kang, Hyekyung Ju, David S Wiley, Irinna Papangeli, Jinah Han, Jun-Dae Kim, William P Dunworth, Xiaoyue Hu, Seyoung Lee, Omar El-Hely, Avraham Sofer, Boryeong Pak, Laura Peterson, Suzy Comhair, Eun Mi Hwang, Jae-Yong Park, Jean-Léon Thomas, Victoria L Bautch, Serpil C Erzurum, Hyung J Chun, Suk-Won Jin
Background -Bone Morphogenetic Protein (BMP) signaling has multiple roles in the development and function of the blood vessels. In humans, mutations in BMP type 2 receptors (BMPR2), a key component of BMP signaling, have been identified in the majority of patients with familial pulmonary arterial hypertension (PAH). However, only a small subset of individuals with BMPR2 mutation develops PAH, suggesting that additional modifiers of BMPR2 function play an important role in the onset and progression of PAH. Methods -We utilized a combination of studies in zebrafish embryos and genetically engineered mice lacking endothelial expression of Vegfr3 to determine the interaction between VEGFR3 and BMPR2...
March 29, 2017: Circulation
https://www.readbyqxmd.com/read/28335084/identification-of-new-bmp6-pro-peptide-mutations-in-patients-with-iron-overload
#17
Chiara Piubelli, Annalisa Castagna, Giacomo Marchi, Monica Rizzi, Fabiana Busti, Sadaf Badar, Monia Marchetti, Marco De Gobbi, Antonella Roetto, Luciano Xumerle, Eda Suku, Alejandro Giorgetti, Massimo Delledonne, Oliviero Olivieri, Domenico Girelli
Hereditary Hemochromatosis (HH) is a genetically heterogeneous disorder caused by mutations in at least five different genes (HFE, HJV, TFR2, SLC40A1, HAMP) involved in the production or activity of the liver hormone hepcidin, a key regulator of systemic iron homeostasis. Nevertheless, patients with an HH-like phenotype that remains completely/partially unexplained despite extensive sequencing of known genes are not infrequently seen at referral centers, suggesting a role of still unknown genetic factors. A compelling candidate is Bone Morphogenetic Protein 6 (BMP6), which acts as a major activator of the BMP-SMAD signaling pathway, ultimately leading to the upregulation of hepcidin gene transcription...
June 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28322831/chemical-inhibitors-of-c-met-receptor-tyrosine-kinase-stimulate-osteoblast-differentiation-and-bone-regeneration
#18
Jung-Woo Kim, Mi Nam Lee, Byung-Chul Jeong, Sin-Hye Oh, Min-Suk Kook, Jeong-Tae Koh
The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been recently introduced to negatively regulate bone morphogenetic protein (BMP)-induced osteogenesis. However, the effect of chemical inhibitors of c-Met receptor on osteoblast differentiation process has not been examined, especially the applicability of c-Met chemical inhibitors on in vivo bone regeneration. In this study, we demonstrated that chemical inhibitors of c-Met receptor tyrosine kinase, SYN1143 and SGX523, could potentiate the differentiation of precursor cells to osteoblasts and stimulate regeneration in calvarial bone defects of mice...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28315766/bone-morphogenetic-protein-4-is-overexpressed-in-and-promotes-migration-and-invasion-of-drug-resistant-cancer-cells
#19
Kairui Zhou, Xiaoli Shi, Jinling Huo, Weihua Liu, Dongxiao Yang, Tengjiao Yang, Tiantian Qin, Cong Wang
Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc)...
March 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28299802/bone-morphogenetic-protein-and-notch-signalling-crosstalk-in-poor-prognosis-mesenchymal-subtype-colorectal-cancer
#20
Shazia Irshad, Mukesh Bansal, Paolo Guarnieri, Hayley Davis, Ayman Al Haj Zen, Brygida Baran, Claudia Maria Assunta Pinna, Haseeb Rahman, Sujata Biswas, Chiara Bardella, Rosemary Jeffery, Lai Mun Wang, James Edward East, Ian Tomlinson, Annabelle Lewis, Simon John Leedham
The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes...
June 2017: Journal of Pathology
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