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Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
Chi-Young Yun, Hwajung Choi, Young-Jae You, Jin-Young Yang, Jin-A Baek, Eui-Sic Cho
Dentin is the major part of tooth and formed by odontoblasts. Under the influence of the inner enamel epithelium, odontoblasts differentiate from ectomesenchymal cells of the dental papilla and secrete pre-dentin which then undergo mineralization into dentin. Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) signaling is essential for dentinogenesis; however, the precise molecular mechanisms remain unclear. To understand the role of TGF-β/BMP signaling in odontoblast differentiation and dentin formation, we generated mice with conditional ablation of Smad4, a key intracellular mediator of TGF-β/BMP signaling, using Osr2 or OC-Cre mice...
September 2016: Anatomy & Cell Biology
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
Amaya García de Vinuesa, Matteo Bocci, Kristian Pietras, Peter Ten Dijke
Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs)...
August 15, 2016: Biochemical Society Transactions
Jacqueline A Pfaff, Birgit Boelck, Wilhelm Bloch, Georg-Hubertus Nentwig
INTRODUCTION: Enhancement of bone regeneration is crucial to dental implantology. Growth factors play a significant role during osteogenesis and angiogenesis. Extracorporeal shock wave therapy (ESWT) enhances bone healing; however, no studies have yet been performed in oral implantology. MATERIALS AND METHODS: Twenty patients who underwent bilateral mandibular wisdom tooth removal were included. ESWT was applied to 1 side of the jaw. Blood samples were collected from the peripheral vein (PB), mandibular bone marrow without and with ESWT (BM-/+SW)...
October 2016: Implant Dentistry
Ioannis Eleftherianos, Julio Cesar Castillo, Jelena Patrnogic
Over the past decade important advances have been made in the field of innate immunity; however, our appreciation of the signaling pathways and molecules that participate in host immune responses to parasitic nematode infections lags behind that of responses to microbial challenges. Here we have examined the regulation and immune activity of Transforming Growth Factor-beta (TGF-β) signaling in the model host Drosophila melanogaster upon infection with the nematode parasites Heterorhabditis gerrardi and H. bacteriophora containing their mutualistic bacteria Photorhabdus...
July 25, 2016: Immunobiology
Yuwen Chen, Evelyn Caporali, Matthew Stewart
OBJECTIVES: Bone morphogenetic protein 2 (BMP-2) is critical for skeletal and cartilage development, homeostasis and repair. This study was conducted to clone and characterize equine BMP-2, develop expression constructs for equine BMP-2, and to determine whether BMP-2 can stimulate chondrogenesis of equine synovial membrane-derived progenitor cells (SMPC). METHODS: Equine BMP-2 cDNA was amplified from chondrocyte RNA, and then transferred into an expression plasmid and adenoviral vector...
September 20, 2016: Veterinary and Comparative Orthopaedics and Traumatology: V.C.O.T
Esra Arslan, Thomas Nellesen, Andreas Bayer, Andreas Prescher, Sebastian Lippross, Sven Nebelung, Holger Jahr, Christine Jaeger, Wolf Dietrich Huebner, Horst Fischer, Marcus Stoffel, Mehdi Shakibaei, Thomas Pufe, Mersedeh Tohidnezhad
BACKGROUND: Although there are many studies discussing the etiological and pathological factors leading to both, acute and chronic tendon injuries, the pathophysiology of tendon injuries is still not clearly understood. Although most lesions are uncomplicated, treatment is long and unsatisfactory due to the poor vascularity of tendon tissue. Platelet mediator concentrate (PMC) contains many growth factors derived from platelets, which can promote wound healing. In this study we investigate the effects of PMC on tenocyte proliferation and differentiation in order to provide an experimental basis for tissue regeneration strategies and to develop new treatment concepts...
2016: BMC Musculoskeletal Disorders
Claudia Davenport, Ulf Diekmann, Insa Budde, Nora Detering, Ortwin Naujok
As known from model organisms, such as frog, fish, mouse and chicken, the anterior-posterior patterning of the definitive endoderm (DE) into distinct domains is controlled by a variety of signaling interactions between the DE and its surrounding mesoderm. This includes Wnt/FGFs and BMPs in the posterior half and all-trans-retinoic acid, TGF-β-ligands, Wnt- and BMP-inhibitors in the anterior half of the DE sheet. However, it is currently unclear how these embryonic tissue interactions can be translated into a defined differentiation protocol for human embryonic stem cells...
June 14, 2016: Stem Cells
Lingling Feng, Brandoch Cook, Su-Yi Tsai, Ting Zhou, Brooke LaFlamme, Todd Evans, Shuibing Chen
Sorely missing from the "toolkit" for directed differentiation of stem/progenitor cells are agonists of the BMP-signaling pathway. Using a high-throughput chemical screen, we discovered that PD407824, a checkpoint kinase 1 (CHK1) inhibitor, increases the sensitivity of cells to sub-threshold amounts of BMP4. We show utility of the compound in the directed differentiation of human embryonic stem cells toward mesoderm or cytotrophoblast stem cells. Blocking CHK1 activity using pharmacological compounds or CHK1 knockout using single guide RNA (sgRNA) confirmed that CHK1 inhibition increases the sensitivity to BMP4 treatment...
May 31, 2016: Cell Reports
Insik Hwang, Kyung-Ah Choi, Hang-Soo Park, Hyesun Jeong, Jeong-Ok Kim, Ki-Cheon Seol, Han-Jin Kwon, In-Hyun Park, Sunghoi Hong
Several types of hair loss result from the inability of hair follicles to initiate the anagen phase of the hair regeneration cycle. Modulating signaling pathways in the hair follicle niche can stimulate entry into the anagen phase. Despite much effort, stem cell-based or pharmacological therapies to activate the hair follicle niche have not been successful. Here, we set out to test the effect of neural stem cell (NSC) extract on the hair follicle niche for hair regrowth. NSC extracts were applied to the immortalized cell lines HaCaT keratinocytes and dermal papilla cells (DPCs) and the shaven dorsal skin of mice...
2016: Cell Transplantation
Giuliana Caronia-Brown, Angela Anderegg, Rajeshwar Awatramani
BACKGROUND: Brain size and patterning are dependent on dosage-sensitive morphogen signaling pathways - yet how these pathways are calibrated remains enigmatic. Recent studies point to a new role for microRNAs in tempering the spatio-temporal range of morphogen functions during development. Here, we investigated the role of miR-135a, derived from the mir-135a-2 locus, in embryonic forebrain development. METHOD: 1. We characterized the expression of miR-135a, and its host gene Rmst, by in situ hybridization (ish)...
April 5, 2016: Neural Development
I M Ciller, S Ka Palanisamy, U A Ciller, J R McFarlane
TGF-beta superfamily members including bone morphogenetic proteins (BMPs) and their receptors (BMPR-1A, -1B and -2) have been shown to be important for reproductive function in both males and females, while information on the role of BMPs in males is limited. Functional studies on select BMPs and BMP receptors have demonstrated vital roles for these proteins in somatic and germ cell proliferation, steroidogenesis and overall fertility. In order to gain insight into the importance of these genes during postnatal reproductive development in males, our study was undertaken to specify the distribution of BMP and BMPR mRNA in male reproductive and steroidogenic tissues and quantify these genes in the testis using the mouse as our model...
March 15, 2016: Physiological Research
Chaoju Hua, Zishuai Wang, Jianbing Zhang, Xing Peng, Xinhua Hou, Yalan Yang, Kui Li, Zhonglin Tang
SMAD7 promotes and enhances skeletal muscle differentiation by inhibiting transforming growth factor beta (TGF-β)/activin signaling and bone morphogenetic protein (BMP) pathways. However, its function, the mechanism regulating its translation, and its association with production meat traits remain unclear in pigs. In this study, we explored SMAD7 gene spatio-temporal and tissue distribution, conducted a single nucleotide polymorphism association analysis, and examined regulation of its expression during skeletal muscle development...
April 2016: Molecular Biology Reports
Henry C J Goodier, Andrew J Carr, Sarah J B Snelling, Lucy Roche, Kim Wheway, Bridget Watkins, Stephanie G Dakin
BACKGROUND: Diseased tendons are characterised by fibrotic scar tissue, which adversely affects tendon structure and function and increases the likelihood of re-injury. The mechanisms and expression profiles of fibrosis in diseased tendon is understudied compared to pulmonary and renal tissues, where transforming growth factor (TGF)β and its associated superfamily are known to be key drivers of fibrosis and modulate extracellular matrix homeostasis. We hypothesised that differential expression of TGFβ superfamily members would exist between samples of human rotator cuff tendons with established disease compared to healthy control tendons...
2016: Arthritis Research & Therapy
Kenichi Mishima, Hiroshi Kitoh, Bisei Ohkawara, Tatsuya Okuno, Mikako Ito, Akio Masuda, Naoki Ishiguro, Kinji Ohno
The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-β) activated kinase-1 (TAK1)-p38 mitogen-activated protein kinase (MAPK) pathway...
December 2015: EBioMedicine
Rafał Stojko, Monika Bojdys-Szyndlar, Agnieszka Drosdzol-Cop, Andrzej Madej, Krzysztof Wilk
The aim of the study was to compare the biological activity of the total pool of genes in CD34(-) umbilical cord blood and bone marrow stem cells and to search for the differences in signaling pathway gene expression responsible for the biological processes. The introductory analysis revealed a big similarity of gene expression among stem cells. When analyzing GO terms for biological processes, we observed an increased activity of JAK-STAT signaling pathway, calcium-mediated, cytokine-mediated, integrin-mediated signaling pathway, and MAPK in a cluster of upregulating genes in CD34(-) umbilical cord blood stem cells...
2016: Stem Cells International
Mona M Zoheiry, Shaimaa Aa Hasan, Eman El-Ahwany, Faten M Nagy, Hoda Abu Taleb, Mona Nosseir, Mona Magdy, Safa Meshaal, Mohamed Darwish El-Talkawy, Inas Raafat
INTRODUCTION: Hepatitis C virus (HCV) is a major cause of chronic liver disease in Egypt, leading to hepatic fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM). Newly-recognized pathogenic mechanisms point to the epithelial-mesenchymal transition (EMT) of hepatocytes to matrix synthesizing (myo-) fibroblasts. Transforming growth factor-beta (TGF-β1), bone morphogenic protein (BMP)-7, and connective tissue growth factor (CTGF) are biomarkers reflecting the EMT process...
December 2015: Electronic Physician
Arash Moghaddam, Lisa Breier, Patrick Haubruck, Daniel Bender, Bahram Biglari, Andreas Wentzensen, Gerald Zimmermann
BACKGROUND: In this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing. METHODS: Our study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions...
2016: Journal of Inflammation
Lovorka Grgurevic, Gitte Lund Christensen, Tim J Schulz, Slobodan Vukicevic
Bore morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)-β superfamily, a group of secreted proteins that regulate embryonic development. This review summarizes the effects of BMPs on physiological processes not exclusively linked to the musculoskeletal system. Specifically, we focus on the involvement of BMPs in inflammatory disorders, e.g. fibrosis, inflammatory bowel disease, anchylosing spondylitis, rheumatoid arthritis. Moreover, we discuss the role of BMPs in the context of vascular disorders, and explore the role of these signalling proteins in iron homeostasis (anaemia, hemochromatosis) and oxidative damage...
February 2016: Cytokine & Growth Factor Reviews
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