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BMP AND smad

Karen Beets, Michael W Staring, Nathan Criem, Elke Maas, Niels Schellinx, Susana M Chuva de Sousa Lopes, Lieve Umans, An Zwijsen
BACKGROUND: Bone morphogenetic protein (BMP) signalling has emerged as a fundamental pathway in endothelial cell biology and deregulation of this pathway is implicated in several vascular disorders. BMP signalling output in endothelial cells is highly context- and dose-dependent. Phosphorylation of the BMP intracellular effectors, SMAD1/5/9, is routinely used to monitor BMP signalling activity. To better understand the in vivo context-dependency of BMP-SMAD signalling, we investigated differences in BMP-SMAD transcriptional activity in different vascular beds during mouse embryonic and postnatal stages...
October 10, 2016: BMC Developmental Biology
Roy Baas, Ayestha Sijm, Hetty A A M van Teeffelen, Robert van Es, Harmjan R Vos, H Th Marc Timmers
Gene-specific transcription factors (GSTFs) control gene transcription by DNA binding and specific protein complex recruitment, which regulates promoter accessibility for transcription initiation by RNA polymerase II. Mutations in the GSTFs Suppressor of Mothers Against Decapentaplegic 2 (SMAD2) and SMAD4 are frequently associated with colon and rectal carcinomas. These proteins play an important role in bone morphogenic protein (BMP) and transforming growth factor β (TGF-β) signaling pathways controlling cell fate and proliferation...
October 4, 2016: Journal of Biological Chemistry
Ujjal K Bhawal, Ryoichiro Uchida, Noboru Kuboyama, Tetsuo Asakura, Koichi Hiratuska, Norihiro Nishiyama
Existing scaffolds cannot adequately satisfy the simultaneous requirements for the regeneration of bone. The challenge remains of how to improve the integration of newly formed bone with the surrounding tissues. The purpose of this study was to investigate the effects of two silk fibroin scaffolds, a hexafluoro isopropanol-based silk fibroin (HFIP-F) and an aqueous-based silk fibroin (A-F), for their osteoinductive potentials in large critical size bone defects in vivo. β-tricalcium phosphate (β-TCP) was used as a positive control...
September 28, 2016: Bio-medical Materials and Engineering
Xinjun Chen, Jing Xu, Baozhou Jiang, Danping Liu
BACKGROUND This aim of this study was to investigate the expression of BMP-7 in atrial fibrillation and illuminate the role of BMP-7 and TGF-β/Smads signaling in myocardial fibrosis. MATERIAL AND METHODS Fibrosis of myocardial fibroblasts was induced by TGF-β1 and the optimal condition was determined by the MTT assay. Cells with TGF-β1 treatment were sub-divided into 4 groups: TGF-β1 group, TGF-β1 + Smad3 siRNA group, TGF-β1 + BMP-7 group, and TGF-β1 + BMP-7 + Smad1/5 siRNA group. Cells were then analyzed by detecting the expression of epithelial cadherin (E-cadherin), collagen I, alpha smooth muscle cell actin (α-SMA), and activated Smads using Western blot...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Wencai Shi, Heyang Wang, Xuan Zheng, Xin Jiang, Zheng Xu, Hui Shen, Min Li
Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4α (HNF-4α) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4α on hepcidin expression was observed by transfecting specific HNF-4α small interfering RNA (siRNA) or plasmids into HepG2 cells...
September 23, 2016: Biological Trace Element Research
Byul-Nim Ahn, Fatih Karadeniz, Chang-Suk Kong, Ki-Ho Nam, Mi-Soon Jang, Youngwan Seo, Han Seong Kim
Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM...
September 14, 2016: Marine Drugs
Huang Fang, PeiWen Song, CaiLiang Shen, XiaoYing Liu, HaiTai Li
OBJECTIVES: In this study, we aimed to investigate the effect of bone mesenchymal stem cells (BMSCs) conditioned medium on BMP4-induced activation of the Smad signaling pathway during the process of neural stem cells differentiation. METHODS: We designed four experimental groups: (A) control group, (B) BMP-4 treatment group, (C) BMSC-CM group, and (D) BMSC-CM (BMSC-conditioned medium) combined with BMP-4 group. The expression of microtube-associated protein-2 (MAP-2) detected by immunocytochemical staining and western blot...
September 16, 2016: Neurological Research
Flora Gilde, Laure Fourel, Raphael Guillot, Isabelle Pignot-Paintrand, Takaharu Okada, Vincent Fitzpatrick, Thomas Boudou, Corinne Albiges-Rizo, Catherine Picart
: Surface coatings delivering BMP are a promising approach to render biomaterials osteoinductive. In contrast to soluble BMPs which can interact with their receptors at the dorsal side of the cell, BMPs presented as an insoluble cue physically bound to a biomimetic matrix, called here matrix-bound (bBMP-2), are presented to cells by their ventral side. To date, BMP-2 internalization and signaling studies in cell biology have always been performed by adding soluble (sBMP-2) to cells adhered on cell culture plates or glass slides, which will be considered here as a "reference" condition...
September 12, 2016: Acta Biomaterialia
L Zhang, P Wang, Y Qin, Q Cong, C Shao, Z Du, X Ni, P Li, K Ding
Galectin-3 (Gal-3) has been implicated in pancreatic ductal adenocarcinoma (PDAC), and its candidacy as a therapeutic target has been evaluated. Gal-3 is widely upregulated in tumors, and its expression is associated with the development and malignancy of PDAC. In the present study, we demonstrate that a polysaccharide, RN1, purified from the flower of Panax notoginseng binds to Gal-3 and suppresses its expression. In addition, RN1 markedly inhibits PDAC cells growth in vitro, in vivo and in patient-derived xenografts...
September 12, 2016: Oncogene
Shuang Cui, Peng-Yu Chang
In mammals, the intestinal epithelium is a tissue that contains two distinct pools of stem cells: active intestinal stem cells and reserve intestinal stem cells. The former are located in the crypt basement membrane and are responsible for maintaining epithelial homeostasis under intact conditions, whereas the latter exhibit the capacity to facilitate epithelial regeneration after injury. These two pools of cells can convert into each other, maintaining their quantitative balance. In terms of the active intestinal stem cells, their development into functional epithelium is precisely controlled by the following signaling pathways: Wnt/β-catenin, Ras/Raf/Mek/Erk/MAPK, Notch and BMP/Smad...
August 21, 2016: World Journal of Gastroenterology: WJG
Atilgan Yilmaz, Chandramohan Kattamuri, Rana N Ozdeslik, Carolyn Schmiedel, Sarah Mentzer, Christoph Schorl, Elena Oancea, Thomas B Thompson, Justin R Fallon
Bone morphogenetic proteins (BMPs) function in most tissues but have cell type-specific effects. Given the relatively small number of BMP receptors, this exquisite signaling specificity requires additional molecules to regulate this pathway's output. The receptor tyrosine kinase MuSK (muscle-specific kinase) is critical for neuromuscular junction formation and maintenance. Here, we show that MuSK also promotes BMP signaling in muscle cells. MuSK bound to BMP4 and related BMPs with low nanomolar affinity in vitro and to the type I BMP receptors ALK3 and ALK6 in a ligand-independent manner both in vitro and in cultured myotubes...
2016: Science Signaling
Xu Yang, Hui Huo, Chunyu Xiu, Miao Song, Yanfei Han, Yanfei Li, Yanzhu Zhu
Bone morphogenetic protein-2 (BMP-2)/Smad signaling pathway plays an important role in regulating osteoblast (OB) differentiation. OB differentiation is a key process of bone formation. Aluminum (Al) exposure inhibits bone formation and causes Al-induced bone disease. However, the mechanism is not fully understood. To investigate whether BMP-2/Smad signaling pathway is associated with OB differentiation in aluminum trichloride (AlCl3)-treated OBs, the primary rat OBs were cultured and exposed to 0 (control group, CG), 1/40 IC50 (low-dose group, LG), 1/20 IC50 (mid-dose group, MG), and 1/10 IC50 (high-dose group, HG) of AlCl3 for 24 h, respectively...
September 4, 2016: Food and Chemical Toxicology
Hugo Urrutia, Abigail Aleman, Edward Eivers
Bone morphogenetic proteins (BMPs) are growth factors that provide essential signals for normal embryonic development and adult tissue homeostasis. A key step in initiating BMP signaling is ligand induced phosphorylation of receptor Smads (R-Smads) by type I receptor kinases, while linker phosphorylation of R-Smads has been shown to cause BMP signal termination. Here we present data demonstrating that the phosphatase Dullard is involved in dephosphorylating the Drosophila R-Smad, Mad, and is integral in controlling BMP signal duration...
2016: Scientific Reports
Mengrui Wu, Guiqian Chen, Yi-Ping Li
Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis...
2016: Bone Research
Yang Cao, Elyse B Mitchell, Jerome L Gorski, Cassandra Hollinger, Nicole L Hoppman
Here, we report strong evidence for a role of the FNDC3B gene in craniofacial development. Chromosomal microarray identified deletions at 3q26.31 in two patients with dysmorphic facial features. Parental FISH studies demonstrated that they are de novo; therefore, these two 3q26.31 microdeletions likely contribute to the patients' dysmorphic features. Interestingly, the minimal region of overlap contains only the FNDC3B gene. Ffibronectin domain III-containing protein 3B (FNDC3B), also known as factor for adipocyte differentiation-104 (FAD104), was first identified as a positive regulator of adipogenesis in a mouse model...
August 19, 2016: American Journal of Medical Genetics. Part A
Emilie Barruet, Blanca M Morales, Wint Lwin, Mark P White, Christina V Theodoris, Hannah Kim, Ashley Urrutia, Sarah Anne Wong, Deepak Srivastava, Edward C Hsiao
BACKGROUND: The Activin A and bone morphogenetic protein (BMP) pathways are critical regulators of the immune system and of bone formation. Inappropriate activation of these pathways, as in conditions of congenital heterotopic ossification, are thought to activate an osteogenic program in endothelial cells. However, if and how this occurs in human endothelial cells remains unclear. METHODS: We used a new directed differentiation protocol to create human induced pluripotent stem cell (hiPSC)-derived endothelial cells (iECs) from patients with fibrodysplasia ossificans progressiva (FOP), a congenital disease of heterotopic ossification caused by an activating R206H mutation in the Activin A type I receptor (ACVR1)...
2016: Stem Cell Research & Therapy
Abdul Soofi, Katherine I Wolf, Egon J Ranghini, Mohammad A Amin, Gregory R Dressler
Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and is increasing with the rising rate of obesity in the developed world. Signaling pathways known to influence the rate of lipid deposition in liver, known as hepatic steatosis, include the transforming growth factor (TGF) superfamily, which function through the SMAD second messengers. The kielin/chordin-like protein (KCP) is a large secreted protein that can enhance bone morphogenetic protein signaling while suppressing TGF-β signaling in cells and in genetically modified mice...
October 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Eun Joo Jeon, Da-Hye Lee, Yang-Ji Kim, Jiyun Ahn, Min Jung Kim, Jin-Taek Hwang, Jinyoung Hur, Mina Kim, Young-Jin Jang, Tae-Youl Ha, Dong-Hyun Seo, Jong Suk Lee, Mi Jeong Sung, Chang Hwa Jung
SCOPE: Yuja (Citrus junos Tanaka) possesses various health benefits, but its effects on bone health are unknown. In this study, the preventative effects of yuja peel ethanol extract (YPEE) on osteopenia were determined in ovariectomized (OVX) rats, and the mechanisms by which YPEE and its flavanones regulate osteoblastogenesis were examined in vitro. METHODS AND RESULTS: The effects of YPEE on osteoblastogenesis were investigated in MC3T3-E1 cells. YPEE promoted alkaline phosphatase (ALP) activity, mineralization, and the expression of osteoblast differentiation marker genes, such as ALP, runt-related transcription factor 2 (Runx2), and osteocalcin (OCN)...
August 9, 2016: Molecular Nutrition & Food Research
Carolina G Santos, Ana Fernandez-Nicolas, Xavier Belles
In contrast with Drosophila melanogaster, practically nothing is known about the involvement of the TGF-β signaling pathway in the metamorphosis of hemimetabolan insects. To partially fill this gap, we have studied the role of Smad factors in the metamorphosis of the German cockroach, Blattella germanica. In D. melanogaster, Mad is the canonical R-Smad of the BMP branch of the TGF-β signaling pathway, Smox is the canonical R-Smad of the TGF-β/Activin branch and Medea participates in both branches. In insects, metamorphosis is regulated by the MEKRE93 pathway, which starts with juvenile hormone (JH), whose signal is transduced by Methoprene-tolerant (Met), which stimulates the expression of Krüppel homolog 1 (Kr-h1) that acts to repress E93, the metamorphosis trigger...
September 1, 2016: Developmental Biology
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...
July 18, 2016: Oncotarget
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