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https://www.readbyqxmd.com/read/28815657/celecoxib-inhibits-osteoblast-differentiation-independent-of-cyclooxygenase-activity
#1
Atsushi Matsuyama, Sen Higashi, Saori Tanizaki, Takahiko Morotomi, Ayako Washio, Tomoko Ohsumi, Chiaki Kitamura, Hiroshi Takeuchi
Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects primarily by inhibiting the activity of cyclooxygenase (COX), thus suppressing prostaglandin synthesis. Some NSAIDs are known to perform functions other than pain control, such as suppressing tumour cell growth, independent of their COX-inhibiting activity. To identify NSAIDs with COX-independent activity, we examined various NSAIDs for their ability to inhibit osteoblastic differentiation using the mouse pre-osteoblast cell line MC3T3-E1. Only celecoxib and valdecoxib strongly inhibited osteoblastic differentiation, and this effect was not correlated with COX-inhibiting activity...
August 16, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28814721/acceleration-of-osteoblast-differentiation-by-a-novel-osteogenic-compound-dmp-pyt-through-activation-of-both-the-bmp-and-wnt-pathways
#2
Su Jung Bae, Hye Joo Kim, Hee Yeon Won, Yong Ki Min, Eun Sook Hwang
Osteoblast differentiation is regulated through the successive activation of signaling molecules by a complex interplay of extracellular signals such as bone morphogenetic protein (BMP) and Wnt ligands. Numerous studies have identified natural as well as synthetic compounds with osteogenic activity through the regulation of either BMP/SMADs or the Wnt/β-catenin pathway. Here, we attempted to isolate small molecules that concurrently activated both SMADs and β-catenin, which led to the discovery of a novel potent osteogenic compound, DMP-PYT...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812969/functional-expression-of-bmp7-receptors-in-oral-epithelial-cells-interleukin-17f-production-in-response-to-bmp7
#3
Kensuke Nishio, Yasumasa Ozawa, Hisanori Ito, Takashi Kifune, Tatsuya Narita, Toshimitsu Iinuma, Nobuhito Gionhaku, Masatake Asano
BACKGROUND: Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily. Recently, BMP7 has been demonstrated to be produced by salivary glands and contribute to embryonic branching in mice. The BMP7 in saliva is thought to be delivered to the oral cavity and is expected to contact with stratified squamous epithelial cells which line the surface of oral mucosa. In this study, we attempted to investigate the effects of BMP7 on oral epithelial cells...
October 2017: Journal of Receptor and Signal Transduction Research
https://www.readbyqxmd.com/read/28805484/disparate-phospho-smad2-levels-in-advanced-type-2-diabetes-patients-with-diabetic-nephropathy-and-early-experimental-db-db-mouse-model
#4
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
Uncontrolled activation of transforming growth factor beta (TGF-β) family members is hypothesized to participate in type 2 diabetes (T2D) dependent diabetic nephropathy (DN). We evaluated and compared downstream activation of the Smad2-signaling pathway in kidney samples from T2D patients to kidneys from the T2D model of leptin receptor deficient db/db mouse. Furthermore, expression of TGF-β family members was evaluated to elucidate molecular mechanisms in the mouse model. Kidney samples from patients with advanced stages of DN showed elevated pSmad2 staining whereas db/db mouse kidneys surprisingly showed a decrease in pSmad2 in the tubular compartment...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#5
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In our previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition state (EMT) and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of HCV core expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28782519/identification-of-novel-alk2-inhibitors-and-their-effect-on-cancer-cells
#6
Minsung Kim, Okran Choi, Suhkneung Pyo, Sang Un Choi, Chi Hoon Park
Bone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, is considered a regulator of glucose homeostasis as well as a neuronal differentiation factor. BMP9 induces phosphorylation of Smad1/5 through activin receptor-like kinase 1 and 2 (ALK1 and ALK2). Recently, many studies have shown that BMP9 contributes to tumorigenesis, and aberrant ALK2 expression is involved in many diseases. To investigate the role of BMP9-ALK2 signaling in cancer cells, we used TF-1 cells that require granulocyte-macrophage colony-stimulating factor (GM-CSF) for cell proliferation...
August 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28761062/t2diacod-a-gene-atlas-of-type-2-diabetes-mellitus-associated-complex-disorders
#7
Jyoti Rani, Inna Mittal, Atreyi Pramanik, Namita Singh, Namita Dube, Smriti Sharma, Bhanwar Lal Puniya, Muthukurussi Varieth Raghunandanan, Ahmed Mobeen, Srinivasan Ramachandran
We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus. They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression. The database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28760815/endothelial-cells-respond-to-the-direction-of-mechanical-stimuli-through-smad-signaling-to-regulate-coronary-artery-size
#8
Aruna Poduri, Brian Raftrey, Andrew H Chang, Siyeon Rhee, Mike Van, Kristy Red-Horse
How mechanotransduction intersects with chemical and transcriptional factors to shape organogenesis is an important question in developmental biology. This is particularly relevant to the cardiovascular system, which uses mechanical signals from flowing blood to stimulate cytoskeletal and transcriptional responses that form a highly efficient vascular network. Using this system, artery size and structure are tightly regulated, but the underlying mechanisms are poorly understood. Here, we demonstrate that deletion of Smad4 increased the diameter of coronary arteries during embryonic development, a phenotype that followed the initiation of blood flow...
July 31, 2017: Development
https://www.readbyqxmd.com/read/28755405/serum-ifn-%C3%AE-predicts-the-therapeutic-effect-of-mesenchymal-stem-cells-transplantation-in-systemic-lupus-erythematosus-patients
#9
Dandan Wang, Shiying Wang, Saisai Huang, Zhuoya Zhang, Xinran Yuan, Xuebing Feng, Liwei Lu, Lingyun Sun
Umbilical cord (UC) derived mesenchymal stem cells (MSCs) show immunoregulatory properties on various immune cells and display therapeutic effects on various autoimmune diseases such as systemic lupus erythematosus (SLE). The aim of this study is to investigate the effect of SLE environment on UC MSCs and to identify the possible serum biomarker to predict the therapeutic effect. UC MSCs were cocultured with peripheral blood mononuclear cells (PBMCs) from active lupus patients and the proliferation, apoptosis and surface markers of UC MSCs were observed...
July 29, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28743897/the-healing-of-alveolar-bone-defects-with-novel-bio-implants-composed-of-ad-bmp9-transfected-rdfcs-and-cha-scaffolds
#10
Li Nie, Xia Yang, Liang Duan, Enyi Huang, Zhou Pengfei, Wenping Luo, Yan Zhang, Xingqi Zeng, Ye Qiu, Ting Cai, Conghua Li
Cells, scaffolds, and growth factors play important roles in bone regeneration. Bone morphogenetic protein 9 (BMP9), a member of BMP family, could facilitate osteogenesis by regulating growth factors and promoting angiogenesis. Similar to other stem cells, rat dental follicle stem cells (rDFCs), the precursor cells of cementoblasts, osteoblasts and periodontal ligament cells, can self-renew and exhibit multipotential capacity. Coralline hydroxyapatite (CHA) has good biocompatibility and conductivity required for bone tissue engineering...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733457/role-of-bone-morphogenetic-proteins-in-sprouting-angiogenesis-differential-bmp-receptor-dependent-signaling-pathways-balance-stalk-vs-tip-cell-competence
#11
Andreas Benn, Christian Hiepen, Marc Osterland, Christof Schütte, An Zwijsen, Petra Knaus
Before the onset of sprouting angiogenesis, the endothelium is prepatterned for the positioning of tip and stalk cells. Both cell identities are not static, as endothelial cells (ECs) constantly compete for the tip cell position in a dynamic fashion. Here, we show that both bone morphogenetic protein (BMP) 2 and BMP6 are proangiogenic in vitro and ex vivo and that the BMP type I receptors, activin receptor-like kinase (ALK)3 and ALK2, play crucial and distinct roles in this process. BMP2 activates the expression of tip cell-associated genes, such as DLL4 (delta-like ligand 4) and KDR (kinase insert domain receptor), and p38-heat shock protein 27 (HSP27)-dependent cell migration, thereby generating tip cell competence...
July 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28731124/bmp7-mediates-the-anticancer-effect-of-honokiol-by-upregulating-p53-in-hct116-cells
#12
Rong-Xing Liu, Wen-Yan Ren, Yan Ma, Yun-Peng Liao, Han Wang, Jia-Hui Zhu, Hai-Tao Jiang, Ke Wu, Bai-Cheng He, Wen-Juan Sun
Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner...
July 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28711939/baicalin-attenuates-monocrotaline-induced-pulmonary-hypertension-through-bone-morphogenetic-protein-signaling-pathway
#13
Zhaohua Zhang, Luan Zhang, Chao Sun, Feng Kong, Jue Wang, Qian Xin, Wen Jiang, Kaili Li, Ou Chen, Yun Luan
Baicalin, a flavonoid compound extracted from roots of Scutellaria baicalensis Georgi (huang qin), it has been shown to effectively attenuates pulmonary hypertension (PH), however, the potential mechanism remains unexplored. In this study, we investigated the potential mechanism of baicalin on monocrotaline (MCT)-induced PH in rats. The results showed that baicalin attenuated lung damage in PH rat model through inhibiting the pulmonary arterial smooth muscle cell proliferation and induction of cells apoptosis...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28711495/evidence-for-constitutive-bone-morphogenetic-protein-2-secretion-by-m1-macrophages-constitutive-auto-paracrine-osteogenic-signaling-by-bmp-2-in-m1-macrophages
#14
Prabhatchandra R Dube, Lutz Birnbaumer, Guillermo Vazquez
Mechanisms mediating vascular calcification recapitulate osteogenic processes encompassing bone formation and imply participation of bone related proteins such as bone morphogenetic protein-2 (BMP-2). Macrophages are amongst the cells that contribute to vascular ossification by releasing cytokines that induce an osteogenic program in vascular smooth muscle cells, and also by becoming themselves osteoclast-like cells. In inflammatory vascular disease, the macrophage population in the vascular wall is diverse, with the M1 or inflammatory, and the M2 or anti-inflammatory macrophage types being dominant...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28703293/bmp-and-tgf%C3%AE-signaling-regulate-the-formation-of-m%C3%A3-ller-glia-derived-progenitor-cells-in-the-avian-retina
#15
Levi Todd, Isabella Palazzo, Natalie Squires, Ninoshka Mendonca, Andy J Fischer
Müller glia-derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell-signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8- and TGFβ/Smad2/3-signaling are coordinated to influence the formation of MGPCs in the chick model system. We find that pSmad1/5/8 is selectively up-regulated in the nuclei of Müller glia following treatment with BMP4, FGF2, or NMDA-induced damage, and this up-regulation is blocked by a dorsomorphin analogue DMH1...
July 13, 2017: Glia
https://www.readbyqxmd.com/read/28697500/cx43-and-smad-mediated-tgf-%C3%AE-bmp-signaling-pathway-promotes-cartilage-differentiation-of-bone-marrow-mesenchymal-stem-cells-and-inhibits-osteoblast-differentiation
#16
Ya-Dong Zhang, Shi-Chang Zhao, Zhong-Sheng Zhu, Yi-Fei Wang, Jian-Xiang Liu, Zhi-Cai Zhang, Feng Xue
BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28687190/a-synthetic-bmp-2-mimicking-peptide-induces-glioblastoma-stem-cell-differentiation
#17
Elena Rampazzo, Monica Dettin, Francesca Maule, Alessandra Scabello, Luisa Calvanese, Gabriella D'Auria, Lucia Falcigno, Elena Porcù, Annj Zamuner, Alessandro Della Puppa, Daniele Boso, Giuseppe Basso, Luca Persano
BACKGROUND: Glioblastoma (GBM) is the most aggressive type of primary brain tumor, characterized by the intrinsic resistance to chemotherapy due to the presence of a highly aggressive Cancer Stem Cell (CSC) sub-population. In this context, Bone Morphogenetic Proteins (BMPs) have been demonstrated to induce CSC differentiation and to sensitize GBM cells to treatments. METHODS: The BMP-2 mimicking peptide, named GBMP1a, was synthesized on solid-phase by Fmoc chemistry...
September 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28684382/a-regulatory-role-of-androgen-in-ovarian-steroidogenesis-by-rat-granulosa-cells
#18
Toru Hasegawa, Yasuhiko Kamada, Takeshi Hosoya, Shiho Fujita, Yuki Nishiyama, Nahoko Iwata, Yuji Hiramatsu, Fumio Otsuka
Excess androgen and insulin-like growth factor (IGF)-I in the ovarian follicle has been suggested to be involved in the pathophysiology of polycystic ovary syndrome (PCOS). Here we investigated the impact of androgen and IGF-I on the regulatory mechanism of ovarian steroidogenesis using rat primary granulosa cells. It was revealed that androgen treatment with dihydrotestosterone (DHT) amplified progesterone synthesis in the presence of FSH and IGF-I, whereas it had no significant effect on estrogen synthesis by rat granulosa cells...
September 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28680581/endothelial-follistatin-like-1-regulates-the-postnatal-development-of-the-pulmonary-vasculature-by-modulating-bmp-smad-signaling
#19
Navessa P Tania, Harm Maarsingh, I Sophie T Bos, Andrea Mattiotti, Stuti Prakash, Wim Timens, Quinn D Gunst, Luis J Jimenez-Borreguero, Martina Schmidt, Maurice J B van den Hoff, Reinoud Gosens
Bone morphogenetic protein (BMP) signaling regulates vascular smooth muscle maturation, endothelial cell proliferation, and tube formation. The endogenous BMP antagonist Follistatin-like 1 (Fstl1) is highly expressed in pulmonary vascular endothelium of the developing mouse lung, suggesting a role in pulmonary vascular formation and vascular homeostasis. The aim of this study was to investigate the role of Fstl1 in the pulmonary vascular endothelium. To this aim, Fstl1 was conditionally deleted from endothelial and endothelial-derived cells using Tie2-cre driven Fstl1-KO mice (Fstl1-eKO mice)...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28679949/aml-induced-osteogenic-differentiation-in-mesenchymal-stromal-cells-supports-leukemia-growth
#20
V Lokesh Battula, Phuong M Le, Jeffrey C Sun, Khoa Nguyen, Bin Yuan, Ximin Zhou, Sonali Sonnylal, Teresa McQueen, Vivian Ruvolo, Keith A Michel, Xiaoyang Ling, Rodrigo Jacamo, Elizabeth Shpall, Zhiqiang Wang, Arvind Rao, Gheath Al-Atrash, Marina Konopleva, R Eric Davis, Melvyn A Harrington, Catherine W Cahill, Carlos Bueso-Ramos, Michael Andreeff
Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, in particular in osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter the BM microenvironment to create a hospitable niche. Here, we report that acute myeloid leukemia (AML) cells, but not normal CD34+ or CD33+ cells, induce osteogenic differentiation in mesenchymal stromal cells (MSCs). In addition, AML cells inhibited adipogenic differentiation of MSCs. Mechanistic studies identified that AML-derived BMPs activate Smad1/5 signaling to induce osteogenic differentiation in MSCs...
July 6, 2017: JCI Insight
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