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C Tsentidis, D Gourgiotis, L Kossiva, A Marmarinos, A Doulgeraki, K Karavanaki
: Higher levels of Dickkopf-1, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, could be indicative of downregulated Wnt system, with possible lower osteoblast activation and higher osteoclast signaling in type 1 diabetes mellitus children and adolescents. Dickkopf-1 could significantly contribute to diabetes osteopathy. INTRODUCTION: Increased fracture risk and elevated Dickkopf-1 levels, which is an inhibitor of Wnt/β-catenin bone metabolic pathway, have been documented in adult patients with type 2 diabetes mellitus (T2D), while no relevant data exist on childhood type 1 diabetes (T1D)...
October 20, 2016: Osteoporosis International
Leilei Zhong, Xiaobin Huang, Emilie Dooms Rodrigues, Jeroen Leijten, Theo Verrips, Mohamed El Khattabi, Marcel Karperien, Janine N Post
Hypertrophic differentiation occurs during in vitro chondrogenesis of mesenchymal stem cells (MSCs), decreasing the quality of the cartilage construct. Previously we identified WNT pathway antagonists Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) as key factors in blocking hypertrophic differentiation of hMSCs. In this study, we investigated the role of endogenously expressed DKK1 and FRZB in chondrogenesis of hMSC, chondrocyte redifferentiation and in preventing cell hypertrophy using three relevant human cell based systems, isolated hMSCs, isolated primary human chondrocytes (hChs), and co-cultures of hMSCs with hChs for which we specifically designed neutralizing nano-antibodies...
October 12, 2016: Stem Cells and Development
Maria Felicia Faienza, Annamaria Ventura, Maurizio Delvecchio, Anna Fusillo, Laura Piacente, Gabriella Aceto, Graziana Colaianni, Silvia Colucci, Luciano Cavallo, Maria Grano, Giacomina Brunetti
CONTEXT: Childhood type 1 diabetes (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors which regulate bone formation. OBJECTIVE: To evaluate sclerostin and DKK-1 levels in TD1M children and to analyze the influence of the glycaemic control on bone health. DESIGN AND SETTING: Cross-sectional study conducted at a clinical research center. Partecipants: One hundred and six T1DM subjects (12.2 ± 4 years), 66 on multiple daily injections (MDI) and 40 on continuous subcutaneous infusion of insulin (CSII), and 80 controls...
October 12, 2016: Journal of Clinical Endocrinology and Metabolism
Hong Peng, Yongguo Li, Yunzhi Liu, Jingnan Zhang, Ke Chen, Ailong Huang, Hua Tang
Numerous evidences suggested that the hepatitis B virus (HBV) was recognized as an important factor in the development of hepatocellular carcinoma (HCC). Dickkopf-1 (DKK1) recently was reported to be involved in the progress of HCC. HBV may regulate DKK1 expression in hematoma carcinogenesis. Here, we demonstrated that HBV could regulate DKK1 promoter activity which resulted in upregulation of its mRNA and protein expression in several HBV existing cell lines, and HBx played a prominent role in this process...
October 10, 2016: Acta Biochimica Polonica
Francesca Santilli, Rossella Liani, Patrizia Di Fulvio, Gloria Formoso, Paola Simeone, Romina Tripaldi, Thor Ueland, Pål Aukrust, Giovanni Davì
Resistin is an adipokine that promotes inflammation and insulin resistance by targeting several cells including platelets. We hypothesised that in type 2 diabetes (T2DM), resistin may foster in vivo oxidative stress, thromboxane-dependent platelet activation and platelet-derived inflammatory proteins release, key determinants of atherothrombosis. A cross-sectional comparison of circulating resistin, sCD40L, as a marker of platelet-mediated inflammation, asymmetric dimethylarginine (ADMA), endothelial dysfunction marker, Dickkopf (DKK)-1, reflecting the inflammatory interaction between platelets and endothelial cells, and urinary 8-iso-PGF2α and 11-dehydro-TxB2, reflecting in vivo lipid peroxidation and platelet activation, respectively, was performed between 79 T2DM patients and 30 healthy subjects...
October 6, 2016: Thrombosis and Haemostasis
Giuseppina Federico, Michael Meister, Daniel Mathow, Gunnar H Heine, Gerhard Moldenhauer, Zoran V Popovic, Viola Nordström, Annette Kopp-Schneider, Thomas Hielscher, Peter J Nelson, Franz Schaefer, Stefan Porubsky, Danilo Fliser, Bernd Arnold, Hermann-Josef Gröne
Renal tubular atrophy and interstitial fibrosis are common hallmarks of etiologically different progressive chronic kidney diseases (CKD) that eventually result in organ failure. Even though these pathological manifestations constitute a major public health problem, diagnostic tests, as well as therapeutic options, are currently limited. Members of the dickkopf (DKK) family, DKK1 and -2, have been associated with inhibition of Wnt signaling and organ fibrosis. Here, we identify DKK3 as a stress-induced, tubular epithelia-derived, secreted glycoprotein that mediates kidney fibrosis...
January 21, 2016: JCI Insight
Kalliopi Klavdianou, Stamatis-Nick Liossis, Lazaros Sakkas, Dimitrios Daoussis
BACKGROUND: Dickkopf-1 (Dkk-1) is a soluble inhibitor of the canonical Wnt pathway, which plays critical roles in embryonic development. Evidence suggests that this molecule regulates several aspects of both bone biology and fibrosis. OBJECTIVES: To provide an overview of our current knowledge of the role of Dkk-1 in joint remodeling and fibrosis. METHODS: We performed an electronic search (Medline) using the following key words: Dickkopf-1 (or Dkk-1), new bone formation, joint remodeling, ankylosing spondylitis, systemic sclerosis (or scleroderma), and fibrosis, supplemented by a manual search of references from retrieved articles...
August 23, 2016: Seminars in Arthritis and Rheumatism
Jung-Hoo Hwang, Jong Cheon Joo, Dae Joon Kim, Eunbi Jo, Hwa-Seung Yoo, Kyung-Bok Lee, Soo Jung Park, Ik-Soon Jang
Constitutive activation of extracellular signal regulated kinase (ERK)-Jun NH2-terminal kinase (JNK) signaling commonly occurs in tumors. The activation of ERK promotes cell proliferation, whereas that of JNK induces cell apoptosis. However, the apoptotic mechanism of ERK-JNK signaling in cancer is not well understood. Recently, we identified that apoptosis and activation of the JNK signaling pathway were induced after cordycepin treatment in human renal cancer, suggesting that JNK signaling might contribute to TK-10 cell apoptosis...
2016: American Journal of Cancer Research
Tetsuo Oka, Kazuhiko Kurozumi, Yosuke Shimazu, Tomotsugu Ichikawa, Joji Ishida, Yoshihiro Otani, Toshihiko Shimizu, Yusuke Tomita, Masakiyo Sakaguchi, Masami Watanabe, Yasutomo Nasu, Hiromi Kumon, Isao Date
Reduced expression in immortalized cells/Dickkopf-3 (REIC/Dkk-3) is a tumor suppressor and therapeutic gene in many human cancers. Recently, an adenovirus REIC vector with the super gene expression system (Ad-SGE-REIC) was developed to increase REIC/Dkk-3 expression and enhance therapeutic effects compared with the conventional adenoviral vector (Ad-CAG-REIC). In this study, we investigated the in vitro and in vivo effects of Ad-SGE-REIC on malignant glioma. In U87ΔEGFR and GL261 glioma cells, western blotting confirmed that robust upregulation of REIC/Dkk-3 expression occurred in Ad-SGE-REIC-transduced cells, most notably after transduction at a multiplicity of infection of 10...
2016: Scientific Reports
Chi-Hin Wong, You-Jia Li, Yang-Chao Chen
Pancreatic ductal adenocarcinoma (PDAC) is a common pancreatic cancer and the fourth leading cause of cancer death in the United States. Treating this life-threatening disease remains challenging due to the lack of effective prognosis, diagnosis and therapy. Apart from pancreatic duct cells, acinar cells may also be the origin of PDAC. During pancreatitis or combined with activating KRas(G12D) mutation, acinar cells lose their cellular identity and undergo a transdifferentiation process called acinar-to-ductal-metaplasia (ADM), forming duct cells which may then transform into pancreatic intraepithelial neoplasia (PanIN) and eventually PDAC...
August 21, 2016: World Journal of Gastroenterology: WJG
Xiang-de Shi, Xian-Huan Yu, Wen-Rui Wu, Xiao-Lin Xu, Jie-Yu Wang, Lei-Bo Xu, Rui Zhang, Chao Liu
Dickkopf-1 (DKK1) is involved in tumorigenesis and the invasion of several tumors. However, its biological function in human hilar cholangiocarcinoma (HCCA) has not yet been documented. This study was designed to investigate the clinical significance and biological function of DKK1 in HCCA. The expression of DKK1 was investigated in thirty-seven human HCCA biopsy samples by immunohistochemistry. To further explore the biological effects of DKK1 in HCCA, transient and stable knockdown of DKK1 in two human HCCA cells (QBC939 and FRH0201) were established using small interfering or short hairpin RNA expression vector...
September 6, 2016: Oncotarget
Chrysoula G Liakou, George Mastorakos, Konstantinos Makris, Ioannis G Fatouros, Alexandra Avloniti, Helen Marketos, Julia D Antoniou, Antonios Galanos, Ismene Dontas, Demetrios Rizos, Symeon Tournis
Studies in postmenopausal women have identified sclerostin as a strong candidate for mediating estrogen effects on the skeleton. The effects of estradiol on sclerostin and Dickkopf-1 in younger women remain unclear. The main purpose of this study is to investigate the impact of estradiol and gonadotrophins fluctuations during the menstrual cycle on circulating sclerostin and Dickkopf-1 levels and the possible relationship of sclerostin and Dickkopf-1 with changes in N-terminal propeptide of type 1 collagen and C-telopeptide of collagen cross-links...
September 6, 2016: Endocrine
Aude Marzo, Soledad Galli, Douglas Lopes, Faye McLeod, Marina Podpolny, Margarita Segovia-Roldan, Lorenza Ciani, Silvia Purro, Francesca Cacucci, Alasdair Gibb, Patricia C Salinas
Synapse degeneration occurs early in neurodegenerative diseases and correlates strongly with cognitive decline in Alzheimer's disease (AD). The molecular mechanisms that trigger synapse vulnerability and those that promote synapse regeneration after substantial synaptic failure remain poorly understood. Increasing evidence suggests a link between a deficiency in Wnt signaling and AD. The secreted Wnt antagonist Dickkopf-1 (Dkk1), which is elevated in AD, contributes to amyloid-β-mediated synaptic failure. However, the impact of Dkk1 at the circuit level and the mechanism by which synapses disassemble have not yet been explored...
October 10, 2016: Current Biology: CB
S Ray, T El Khassawna, U Sommer, U Thormann, N D Wijekoon, K Lips, C Heiss, V Alt
Wnt/β-catenin signalling components was shown to affect bone cells function including chondrocytes.Secreted Dkk1, a potent osteogenesis inhibiting factor mediates bone loss in diseased bones by suppressing the biological actions of Wnt proteins. In addition, increased Dkk1 signalling inhibits chondrogenesis in new bone formation. Recent findings also show there exists a cross-talk between the chondrocytes and the cells of the osteoblast lineage, which are the most affected cell types in muskuloskeletal disorders...
August 31, 2016: Journal of Microscopy
Yu Chen, Zi-Feng Chen, Fan He
OBJECTIVE: To understand the mechanism by which tenascin-C regulates osteoblast differentiation and the role of tenascin-C in osteoporosis. METHODS: Tenascin-C protein expression in femoral spongy bone of mice with or without osteoporosis was analyzed using Western blotting. In MC3T3-E1 osteoblasts with or without tenascin-C depletion by a specific siRNA targeting tenascin-C, alkaline phosphatase activity and Dickkopf-1 (DKK-1) expression were determined using quantitative RT-PCR and Western blotting, and the transcriptional activity of Wnt signaling pathway was analyzed using a luciferase reporter assay...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Xin-Wei He, En Wang, Yu-Yan Bao, Feng Wang, Ming Zhu, Xiao-Fei Hu, Xiao-Ping Jin
BACKGROUND AND AIMS: Sclerostin and Dickkopf-1 (Dkk-1) are potent antagonists of Wnt signalling and might therefore play important roles in cardiovascular disease. We investigated whether serum sclerostin and Dkk-1 levels are associated with acute ischaemic stroke and specific stroke subtypes. METHODS: Serum levels of sclerostin and Dkk-1 were measured by ELISA on day 1 and on day 6 after stroke in 62 patients with large artery atherosclerotic (LAA) stroke, on day 1 after stroke in 62 age- and gender-matched patients with small-artery occlusion (SAO) stroke and on admission in 62 healthy controls...
October 2016: Atherosclerosis
Hongxia Zhang, Weili Luo, Yonghong Sun, Yanchun Qiao, Liying Zhang, Zhilian Zhao, Shijun Lv
Increasing studies identified podocyte injury as a key early risk factor resulting in diabetic nephropathy (DN). The ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) participates in podocyte differentiation and injury, which is elevated in the podocytes of a variety of nephritis. Whether UCH-L1 expression is positively related to podocyte injury of DN remains unclear. In this study, elevated expression of UCH-L1 and its intrinsic mechanism in high glucose (HG)-stimulated murine podocytes were investigated using western blot and real-time quantitative PCR...
2016: International Journal of Molecular Sciences
Li-Ye Sun, Zi-Dong Bie, Chuan-Huan Zhang, Hua Li, Liu-Dong Li, Jun Yang
Excessive proliferation of cardiac fibroblasts (CFs) and their transdifferentiation into myofibroblasts leads to expression of α-smooth muscle actin (α-SMA), as well as excessive synthesis and secretion of collagens. This process represents an important pathological basis for myocardial fibrosis (MF). MicroRNA (miR)-154 and the Wnt signaling pathway play key roles in the above process, although their specific interactions are poorly understood. After transfecting CFs with miR-154 mimics or inhibitors, miR-154 was found to inhibit the expression of Dickkopf-related protein 2 (DKK2), while miR-154 inhibitors upregulated DKK2 expression in a western blot analysis...
August 20, 2016: Cell Biology International
F Linke, M Harenberg, M M Nietert, S Zaunig, F von Bonin, A Arlt, M Szczepanowski, H A Weich, S Lutz, C Dullin, P Janovská, M Krafčíková, L Trantírek, P Ovesná, W Klapper, T Beissbarth, F Alves, V Bryja, L Trümper, J Wilting, D Kube
The interaction between vascular endothelial cells (ECs) and cancer cells is of vital importance to understand tumor dissemination. A paradigmatic cancer to study cell-cell interactions is classical Hodgkin Lymphoma (cHL) owing to its complex microenvironment. The role of the interplay between cHL and ECs remains poorly understood. Here we identify canonical WNT pathway activity as important for the mutual interactions between cHL cells and ECs. We demonstrate that local canonical WNT signaling activates cHL cell chemotaxis toward ECs, adhesion to EC layers and cell invasion using not only the Wnt-inhibitor Dickkopf, tankyrases and casein kinase 1 inhibitors but also knockdown of the lymphocyte enhancer binding-factor 1 (LEF-1) and β-catenin in cHL cells...
October 4, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Letteria Minutoli, Mariagrazia Rinaldi, Herbert Marini, Natasha Irrera, Giovanni Crea, Cesare Lorenzini, Domenico Puzzolo, Andrea Valenti, Antonina Pisani, Elena B Adamo, Domenica Altavilla, Francesco Squadrito, Antonio Micali
Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis...
2016: International Journal of Molecular Sciences
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