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Tianda Chen, Qinwei Wu, Yang Zhang, Tianlan Lu, Weihua Yue, Dai Zhang
Background: Transcription factor 4 (TCF4) is found to be associated with schizophrenia. TCF4 mutations also cause Pitt-Hopkins Syndrome, a neurodevelopmental disorder associated with severe mental retardation. However, the function of TCF4 during brain development remains unclear. Results: Here, we report that Tcf4 is expressed in the developing cerebral cortex. In utero suppression of Tcf4 arrested neuronal migration, leading to accumulation of ectopic neurons in the intermediate zone. Knockdown of Tcf4 impaired leading process formation...
2016: Frontiers in Molecular Neuroscience
Laura Hildebrand, Katja Stange, Alexandra Deichsel, Manfred Gossen, Petra Seemann
Patients with Fibrodysplasia Ossificans Progressiva (FOP) suffer from ectopic bone formation, which progresses during life and results in dramatic movement restrictions. Cause of the disease are point mutations in the Activin A receptor type 1 (ACVR1), with p.R206H being most common. In this study we compared the signalling responses of ACVR1(WT) and ACVR1(R206H) to different ligands. ACVR1(WT), but not ACVR1(R206H) inhibited BMP signalling of BMP2 or BMP4 in a ligand binding domain independent manner. Likewise, the basal BMP signalling activity of the receptor BMPR1A or BMPR1B was inhibited by ACVR1(WT), but enhanced by ACVR1(R206H)...
October 4, 2016: Cellular Signalling
Elisabetta Bigagli, Carlotta De Filippo, Cinzia Castagnini, Simona Toti, Francesco Acquadro, Francesco Giudici, Marilena Fazi, Piero Dolara, Luca Messerini, Francesco Tonelli, Cristina Luceri
BACKGROUND: DNA copy number alterations (CNAs) and gene expression changes have amply been encountered in colorectal cancers (CRCs), but the extent at which CNAs affect gene expression, as well as their relevance for tumor development, are still poorly defined. Here we aimed at assessing the clinical relevance of these parameters in a 10 year follow-up study. METHODS: Tumors and normal adjacent colon mucosa, obtained at primary surgery from 21 CRC patients, were subjected to (i) high-resolution array CGH (a-CGH) for the detection of CNAs and (ii) microarray-based transcriptome profiling for the detection of gene expression (GE) changes...
October 5, 2016: Cellular Oncology (Dordrecht)
Lucy Cassar, Craig Nicholls, Alex R Pinto, Ruping Chen, Lihui Wang, He Li, Jun-Ping Liu
Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis...
September 30, 2016: Protein & Cell
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Alexandra M Gouveia, Inês O Gonçalves, Sara Becerril, Beatriz Ramírez, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
AIMS: Exercise-stimulated myokine secretion into circulation may be related with browning in white adipose tissue (WAT), representing a positive metabolic effect on whole-body fat mass. However, limited information is yet available regarding the impact of exercise on myokine-related modulation of adipocyte phenotype in WAT from obese rats. MAIN METHODS: Sprague-Dawley rats (n=60) were divided into sedentary and voluntary physical activity (VPA) groups and fed with standard (35kcal% fat) or high-fat (HFD, 71kcal% fat)-isoenergetic diets...
September 27, 2016: Life Sciences
Taro Tsujimura, Mana Idei, Masahiro Yoshikawa, Osamu Takase, Keiichi Hishikawa
The gene encoding bone morphogenetic protein-7 (Bmp7) is expressed in the developing kidney in embryos and also in the mature organ in adults. During kidney development, expression of Bmp7 is essential to determine the final number of nephrons in and proper size of the organ. The secreted BMP7 acts on the nephron progenitor cells to exert its dual functions: To maintain and expand the progenitor population and to provide them with competence to respond to differentiation cues, each relying on distinct signaling pathways...
September 26, 2016: World Journal of Stem Cells
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
Adel Mahmoud, Dalia Fayez, Mervat Mammdouh Abou Gabal, Sherin Mohamed Hosny Hamza, Takwa Badr
INTRODUCTION: Fusion of joints as well as intervertebral spaces by the formation of bony spurs appearing as syndesmophytes and osteophytes are the hallmark of spondyloarthropathies which accounts for disability. The aim of this study was to assess the serum level of bone morphogenetic protein (BMP)-7 in ankylosing spondylitis and its relationship with disease activity and the radiographic damage. METHODS: This longitudinal case control study was conducted in Ain Shams University Hospitals (Egypt)...
July 2016: Electronic Physician
Wendong Ruan, Yuan Xue, Yaqi Zong, Chao Sun
In the present study, third‑generation autologous‑inactivated bone morphogenic protein 2 (BMP2), BMP4, BMP6, BMP7, BMP9 and Wnt3a lentiviral vectors were constructed and integrated into the genome of MC3T3‑E1 murine mesenchymal stem cells (MMSCs) to produce osteoinductive factor gene‑modified MMSCs. The transfection efficiency of each osteoinductive factor was then determined by detecting the expression levels of runt related transcription factor 2 (Runx2) mRNA. The cotransfection with combinations of two lentiviruses was performed, and the expression levels of bone γ‑carboxyglutamate protein and alkaline phosphatase in the MC3T3‑E1 cell culture supernatant were detected...
September 12, 2016: Molecular Medicine Reports
Andrea Schuette, Arash Moghaddam, Petra Seemann, Georg N Duda, Gerhard Schmidmaier, Lutz Schomburg
BACKGROUND: Recombinant human bone morphogenetic protein 7 (rhBMP7) is applied for treatment of bone fractures, especially tibial non-unions. Its application may induce autoantibodies (aAB) affecting the targeted and endogenous signaling pathways and in turn negatively impact treatment efficacy. METHODS: Novel and sensitive assays for the quantification of BMP7-aAB and BMP2-aAB were established and used to analyze serum samples from healthy controls (n = 100 men, n = 100 women) and patients with long bone fracture (n = 265) treated or not with rhBMP7...
December 2016: BBA Clinical
Xiao-Chuan Li, Yao-Hong Wu, Xue-Dong Bai, Wei Ji, Zi-Ming Guo, Chao-Feng Wang, Qing He, Di-Ke Ruan
Tissue engineering has shown great success in the treatment of intervertebral disk degeneration (IVDD) in the past decade. However, the adverse and harsh microenvironment associated in the intervertebral disks remains a great obstacle for the survival of transplanted cells. Although increasing numbers of new materials have been created or modified to overcome this hurdle, a new effective strategy of biological therapy is still required. In this study, bone morphogenic protein 7 (BMP7)-based functionalized self-assembling peptides were developed by conjugating a bioactive motif from BMP-7 (RKPS) onto the C-terminal of the peptide RADARADARADARADA (RADA16-I) at a ratio of 1:1 to form a new RADARKPS peptide...
October 2016: Tissue Engineering. Part A
Hanlu Yin, Yi Wang, Wenping Chen, Shanliang Zhong, Zhian Liu, Jianhua Zhao
High expression of Chemokine receptor 4 (CXCR4) is important in tumor invasion, metastasis, drug-resistance and maintenance of stemness in non-small cell lung cancer (NSCLC). We therefore studied the molecular characteristics of drug-resistant CXCR4-positive cells on epithelial-mesenchymal transition (EMT) for the future identification of the tumor cells with the properties of both EMT and stemness. EMT RT(2) Profier PCR Array was performed to determine the expression levels of mRNA genes in A549 with TGF-β1 induced EMT (A549/TGF-β1) and gefitinib-resistant CXCR4-positive cells (A549/GR)...
December 5, 2016: Gene
X Y Lv, R Ni, W Sun, R Su, H H Musa, J F Yin, Q Z Wang, W Gao, L Chen
The aim of this study was to detect candidate genes for the development of hair follicles in the Hu sheep breed. Seven genes have been detected in large, medium, and small wave follicles of Hu sheep using gene chip technology. The histological features of the follicles of newborn Hu-lambs were combined with fluorescence quantitative PCR technology to detect the correlation between the expression of the seven genes and hair follicle development. Among the genes studied, matrix metalloproteinase 2 (MMP2), bone morphogenetic protein-7 (BMP7), and sideroflexin 1 (SFXN1) showed a significantly different pattern of expression in large, medium, and small wave follicles (P < 0...
2016: Genetics and Molecular Research: GMR
Xiaoyu Liu, Yahong Zhao, Su Peng, Shuqiang Zhang, Meihong Wang, Yeyue Chen, Shan Zhang, Yumin Yang, Cheng Sun
Schwann cell (SC) myelination is pivotal for the proper physiological functioning of the nervous system, but the underlying molecular mechanism remains less well understood. Here, we showed that the expression of bone morphogenetic protein 7 (BMP7) inversely correlates with myelin gene expression during peripheral myelination, which suggests that BMP7 is likely a negative regulator for myelin gene expression. Our experiments further showed that the application of BMP7 attenuates the cAMP induced myelin gene expression in SCs...
2016: Scientific Reports
Akira Satoh, Aki Makanae, Yurie Nishimoto, Kazumasa Mitogawa
Urodele amphibians have a remarkable organ regeneration ability that is regulated by neural inputs. The identification of these neural inputs has been a challenge. Recently, Fibroblast growth factor (Fgf) and Bone morphogenic protein (Bmp) were shown to substitute for nerve functions in limb and tail regeneration in urodele amphibians. However, direct evidence of Fgf and Bmp being secreted from nerve endings and regulating regeneration has not yet been shown. Thus, it remained uncertain whether they were the nerve factors responsible for successful limb regeneration...
September 1, 2016: Developmental Biology
Anna Hyc, Stanislaw Moskalewski, Anna Osiecka-Iwan
Articular cartilage and the synovial membrane both ensure the smooth action of synovial joints; however, the influence of chondrocytes on synovial metabolism remains unclear. The secretory activity of chondrocytes is usually studied in cell cultures and may differ from that in intact cartilage. According to McCutchen's theory of 'weeping' joint lubrication, loading of the articular cartilage during motion squeezes the fluid with lubricating properties from the cartilage. The purpose of the study was to obtain cartilage interstitial fluid (CIF) from intact cartilage and to evaluate its influence on gene expression in the synovial membrane cells...
September 2016: International Journal of Molecular Medicine
Sambad Sharma, Fei Xing, Yin Liu, Kerui Wu, Neveen Said, Radhika Pochampally, Yusuke Shiozawa, Hui-Kuan Lin, K C Balaji, Kounosuke Watabe
Prostate cancer is known to frequently recur in bone; however, how dormant cells switch its phenotype leading to recurrent tumor remains poorly understood. We have isolated two syngeneic cell lines (indolent and aggressive) through in vivo selection by implanting PC3mm stem-like cells into tibial bones. We found that indolent cells retained the dormant phenotype, whereas aggressive cells grew rapidly in bone in vivo, and the growth rates of both cells in culture were similar, suggesting a role of the tumor microenvironment in the regulation of dormancy and recurrence...
September 9, 2016: Journal of Biological Chemistry
Kenji Suzuki, Somasundaram Arumugam, Junji Yokoyama, Yusuke Kawauchi, Yutaka Honda, Hiroki Sato, Yutaka Aoyagi, Shuji Terai, Kazuichi Okazaki, Yasuo Suzuki, Shuji Mizumoto, Kazuyuki Sugahara, Raja Atreya, Markus F Neurath, Kenichi Watanabe, Taishi Hashiguchi, Hiroyuki Yoneyama, Hitoshi Asakura
Induction of mucosal healing (MH) is an important treatment goal in inflammatory bowel disease (IBD). Although the molecular mechanisms underlying MH in IBD is not fully explored, local fibrosis would contribute to interfere mucosal repair. Carbohydrate sulfotransferase 15 (CHST15), which catalyzes sulfation of chondroitin sulfate to produce rare E-disaccharide units, is a novel mediator to create local fibrosis. Here we have used siRNA-based approach of silencing CHST15 in dextran sulfate sodium (DSS) induced colitis in mice, human colon fibroblasts and cancer cell lines...
2016: PloS One
Andrea M Chiariello, Carlo Annunziatella, Simona Bianco, Andrea Esposito, Mario Nicodemi
Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics...
2016: Scientific Reports
Vrinda Sreekumar, Romina Haydeé Aspera-Werz, Gauri Tendulkar, Marie Karolina Reumann, Thomas Freude, Katja Breitkopf-Heinlein, Steven Dooley, Stefan Pscherer, Björn Gunnar Ochs, Ingo Flesch, Valeska Hofmann, Andreas Klaus Nussler, Sabrina Ehnert
Promotion of rhBMP2 and rhBMP7 for the routine use to support fracture healing has been hampered by high costs, safety concerns and reasonable failure rates, imposing restrictions in its clinical use. Since there is little debate regarding its treatment potential, there is rising need for a better understanding of the mode of action of these BMPs to overcome its drawbacks and promote more efficacious treatment strategies for bone regeneration. Recently, BMP9, owing to its improved osteogenic potential, is gaining attention as a promising therapeutic alternative...
July 9, 2016: Archives of Toxicology
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