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Dickkopf AND Wnt

Xiaobin Huang, Janine N Post, Leilei Zhong, Jeroen Leijten, Staffan Larsson, Marcel Karperien, André Struglics
OBJECTIVE: To explore the involvement of the WNT and BMP antagonists Dickkopf-related protein 1 (DKK1), Frizzled-related protein (FRZB) and Gremlin 1 (GREM1) in knee injury and osteoarthritis (OA). DESIGN: The antagonists were immunoassayed in synovial fluid from a cross-sectional cohort of 9 knee healthy reference subjects, patients with recent (0-77 days, n=158) or old (1-37 years, n=50) knee injuries, and OA (n=22). Cartilage (ARGS-aggrecan, cartilage oligomeric matrix protein and C2C type II collagen) and other biomarkers were assessed in synovial fluid in a subset of samples...
March 8, 2018: Osteoarthritis and Cartilage
Ken Kataoka, Natsumi Maehara, Yuki Ayabe, Hitoshi Murata, Nam-Ho Huh, Masakiyo Sakaguchi
Our previous studies revealed that REIC/Dkk-3 was expressed various tissues, including skin keratinocytes. The aim of the present study was to identify the factors that regulate the expression of the dickkopf Wnt signaling pathway inhibitor 3 (REIC/Dkk‑3) tumor suppressor gene in normal human skin keratinocytes (NHKs). Several growth factors and cytokines that have previously been reported to be involved in the growth and differentiation of keratinocytes were screened as potential regulators. Western blot analysis was performed using protein from NHKs cultured with/without various factors including the epidermal growth factor, tumor necrosis factor‑α, transforming growth factor‑β, interleukin (IL)‑1F9, IL‑6, IL‑8 and Ca2+...
March 5, 2018: Molecular Medicine Reports
Eva Z Hoseth, Florian Krull, Ingrid Dieset, Ragni H Mørch, Sigrun Hope, Erlend S Gardsjord, Nils Eiel Steen, Ingrid Melle, Hans-Richard Brattbakk, Vidar M Steen, Pål Aukrust, Srdjan Djurovic, Ole A Andreassen, Thor Ueland
The Wnt signaling pathway plays a crucial role in neurodevelopment and in regulating the function and structure of the adult nervous system. Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders with evidence of subtle neurodevelopmental, structural and functional neuronal abnormalities. We aimed to elucidate the role of aberrant regulation of the Wnt system in these disorders by evaluating plasma levels of secreted Wnt modulators in patients (SCZ = 551 and BD = 246) and healthy controls (HCs = 639) using enzyme immune-assay...
March 6, 2018: Translational Psychiatry
Bushra Parveen, Manjari Tripathi, Divya Vohora
Long-term anti-epileptic drug (AED) therapy compromises bone health. Though vitamin-D deficiency is proposed to be involved, it alone is not held responsible. This accounts for investigating other mechanisms in bone accrual. Recent studies have shown modulation of inhibitors of wnt pathway, sclerostin and dickkopf-1 (DKK-1), in glucocorticoids-induced osteoporosis. We investigated whether AED monotherapy modulates wnt inhibitors in Indian women with epilepsy. Women of age > 20-40 years with the diagnosis of epilepsy and receiving AEDs (carbamazepine, valproate and levetiracetam) for at least a year were enrolled...
March 5, 2018: Basic & Clinical Pharmacology & Toxicology
Z Malik, M Alexiou, B Hallgrimsson, A N Economides, H U Luder, D Graf
Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice...
February 1, 2018: Journal of Dental Research
Lubomir Bodnar, Rafał Stec, Szczepan Cierniak, Agnieszka Synowiec, Gabriel Wcisło, Marzena Jesiotr, Robert Koktysz, Paweł Chrom, Cezary Szczylik
BACKGROUND: The aim of the present study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of the WNT/β-catenin pathway. PATIENTS AND METHODS: In a prospective, single-arm, phase II study, patients with mRCC received everolimus (10 mg/d) in a 30-day cycle. We performed a prospectively planned evaluation of the potential biomarkers of the WNT/β-catenin pathway...
February 2, 2018: Clinical Genitourinary Cancer
Michael K Dame, Durga Attili, Shannon D McClintock, Priya H Dedhia, Peter Ouillette, Olaf Hardt, Alana M Chin, Xiang Xue, Julie Laliberte, Erica L Katz, Gina M Newsome, David R Hill, Alyssa J Miller, Yu-Hwai Tsai, David Agorku, Christopher H Altheim, Andreas Bosio, Becky Simon, Linda C Samuelson, Jay A Stoerker, Henry D Appelman, James Varani, Max S Wicha, Dean E Brenner, Yatrik M Shah, Jason R Spence, Justin A Colacino
The intestine is maintained by stem cells located at the base of crypts and distinguished by the expression of LGR5. Genetically engineered mouse models have provided a wealth of information about intestinal stem cells, while less is known about human intestinal stem cells due to difficulty detecting and isolating these cells. We established an organoid repository from patient-derived adenomas, adenocarcinomas, and normal colon, which we analyzed for variants in 71 colorectal cancer (CRC) associated genes. Normal and neoplastic colon tissue organoids were analyzed by immunohistochemistry and fluorescent-activated cell sorting for LGR5...
February 21, 2018: Development
Jieping Li, Wenlin Gong, Xiaoxue Li, Ruirong Wan, Fengzhen Mo, Zhenghua Zhang, Panpan Huang, Zixi Hu, Zongqiang Lai, Xiaoling Lu, Yongxiang Zhao
Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Multiple etiologic factors such as virus and environment can lead to HCC. It is a challenge for us to successfully detect early HCC due to the lack of effective characterized and specific biomarkers. However, if the early diagnosis is successfully realized, it provides crucial chance for HCC patients to receive effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary glycoprotein, which negatively regulates Wnt pathway through binding to surface receptors LRP5/6 and Kremen 1/2...
August 1, 2018: Journal of Nanoscience and Nanotechnology
Ryan D Ross, Raj C Shah, Sue Leurgans, Teodoro Bottligieri, Robert S Wilson, D Rick Sumner
Background: Osteoporosis and Alzheimer's disease (AD) are common diseases of aging that would seem to be unrelated, but may be linked through the influence of bone-derived signals on brain function. The current study aimed to investigate the relationship between circulating levels of bone-related biomarkers and cognition. Methods: The population included 103 community-dwelling older individuals with memory concerns but without cognitive impairment. A global cognition summary measure was collected at baseline and 6, 12, and 18-months post-enrollment by converting raw scores from 19 cognitive function tests to z-scores and averaging...
February 8, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
February 12, 2018: Nature Medicine
Roelof A J Smit, Johan Wouter Jukema, Iris Postmus, Ian Ford, Pieternella Eline Slagboom, Bastiaan T Heijmans, Saskia Le Cessie, Stella Trompet
In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial...
January 11, 2018: Journal of Clinical Lipidology
Argyrios Sklavos, Theofilos Poutahidis, Alexander Giakoustidis, Kali Makedou, Katerina Angelopoulou, Alexander Hardas, Paola Andreani, Argyro Zacharioudaki, George Saridis, Thomas Goulopoulos, Kalliopi Tsarea, Maria Karamperi, Vassilios Papadopoulos, Vassilios Papanikolaou, Apostolos Papalois, Stavros Iliadis, Satvinder Mudan, Daniel Azoulay, Dimitrios Giakoustidis
Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC. The depletion of Wnt-1 using neutralizing antisera was done for ten consecutive days at the age of 9 months and mice were examined for the following 20 days...
January 2018: Oncology Letters
Zahid Khan, Maha Arafah, Jilani Purusottapatnam Shaik, Alka Mahale, Mohammad Saud Alanazi
Purpose: Breast carcinoma is the most common malignancy and leading cause of cancer-related deaths in women worldwide including Saudi Arabia. Breast cancer in Saudi women develops at a much early age with median age of onset of 49 years compared to 62 years observed in patients from USA. Aberrations in wingless and integration site growth factor (Wnt) signaling pathway have been pathologically implicated in development of breast cancers and hence its role was examined in Saudi patients...
2018: OncoTargets and Therapy
Anita Khadka, Marina Martínez-Bartolomé, Stephanie D Burr, Ryan C Range
The anterior neuroectoderm (ANE) in many deuterostome embryos (echinoderms, hemichordates, urochordates, cephalochordates, and vertebrates) is progressively restricted along the anterior-posterior axis to a domain around the anterior pole. In the sea urchin embryo, three integrated Wnt signaling branches (Wnt/β-catenin, Wnt/JNK, and Wnt/PKC) govern this progressive restriction process, which begins around the 32- to 60-cell stage and terminates by the early gastrula stage. We previously have established that several secreted Wnt modulators of the Dickkopf and secreted Frizzled-related protein families (Dkk1, Dkk3, and sFRP-1/5) are expressed within the ANE and play important roles in modulating the Wnt signaling network during this process...
2018: EvoDevo
Ravisha Wadhwa, Manoj Kumar, Yam Nath Paudel, Ramsha Iqbal, Priyanka Kothari, Ritu Trivedi, Divya Vohora
In view of the opposite effects of gut and brain serotonin in bone, the key role of Wnt β/catenin pathway in osteoblastic proliferation and the controversial bony effects of selective serotonin reuptake inhibitors antidepressants, the present study investigated the effects of escitalopram alone and in combination with carbidopa (to block gut-derived serotonin) on markers of bone turnover and Wnt signaling and micro-CT in male Wistar rats. Escitalopram (2.0 mg/kg, p.o.) and carbidopa (10 mg/kg, p.o.) were administered daily for 40 days following which indicators of reduced (dickkopf-1, sclerostin), and increased (alkaline phosphatase) bone formation and bone resorption markers (receptor activator of nuclear factor κB ligand, tartrate-resistant acid phosphatase 5b) were determined...
January 29, 2018: Journal of Bone and Mineral Metabolism
Manreet Kaur Padwal, Genyang Cheng, Limin Liu, Felix J Boivin, Azim Gangji, Kenneth Scott Brimble, Darren Bridgewater, Peter J Margetts
The WNT signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor beta (TGFB) mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis...
January 24, 2018: American Journal of Physiology. Renal Physiology
Jia-Jia Zhu, Yi-Pu Chen, Min Yang, Bao-Li Liu, Jing Dong, Hong-Rui Dong, Hong-Liang Rui, Hong Cheng
Obesity-related glomerulopathy (ORG) is morphologically characterized by glomerulomegaly with or without observable focal segmental glomerulosclerosis under light microscope, with decreased podocyte density and number, and with increased foot‑process width observed under electron microscope. The severity of podocyte injury is correlated with the degree of proteinuria and renal dysfunction. However, the pathogenesis of ORG is not well understood. The aim of the present study was to explore the possible pathogenic role of aldosterone (ALDO) in ORG...
January 5, 2018: Molecular Medicine Reports
Jiapeng Bao, Chiyuan Ma, Jisheng Ran, Yan Xiong, Shigui Yan, Lidong Wu
To investigate the inflammatory effect of Interleukin 18 (IL-18) on rat chondrocytes and the involvement of Wnt/β-catenin and Hedgehog pathways, the mRNA and protein level of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and chondrocyte-specific proteins (Collagen II and aggrecan) were evaluated by qRT-PCR and Western blot, and key protein level of Wnt/β-catenin and Hedgehog pathways including β-catenin, GSK-3β, DKK-1, IHH, SHH, and Gli-2 were evaluated by Western blot. Dickkopf-1 (DKK-1) and Cyclopamine were used as antagonist of Wnt/β-catenin and Hedgehog pathways to perform pathway inhibition tests...
December 15, 2017: Oncotarget
Eirini Karamariti, Chungang Zhai, Baoqi Yu, Qiao Lei, Zhihong Wang, Claire M F Potter, Mei Mei Wong, Russell M L Simpson, Zhongyi Zhang, Xiaocong Wang, Ivan Del Barco Barrantes, Christof Niehrs, Deling Kong, Qiang Zhao, Yun Zhang, Yanhua Hu, Cheng Zhang, Qingbo Xu
OBJECTIVES: DKK3 (dickkopf 3), a 36-kD secreted glycoprotein, has been shown to be involved in the differentiation of partially reprogrammed cells and embryonic stem cells to smooth muscle cells (SMCs), but little is known about its involvement in vascular disease. This study aims to assess the effects of DKK3 on atherosclerotic plaque composition. APPROACH AND RESULTS: In the present study, we used a murine model of atherosclerosis (ApoE-/-) in conjunction with DKK3-/- and performed tandem stenosis of the carotid artery to evaluate atherosclerotic plaque development...
December 28, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
Ana M Santos, Eugenia-Lucía Saldarriaga, Rodrigo Giraldo-Bustos, Jesus Giovanny Ballesteros-Muñoz, Juan C Rueda, Francy-Milena Cuervo, José-Ignacio Angarita, Andrés Y Vásquez, Sofía Arias-Correal, Camilo A González, Pedro Santos-Moreno, John Londono
Rheumatoid arthritis (RA) is an inflammatory disease characterized by joint destruction, deformity, lower functionality, and decrease in life expectancy. Wingless signaling pathway (Wnt) has been recently involved in bone homeostasis. Studies suggest that overexpression of the pathway inhibitors, like the Dickkopf 1 protein (DKK1), has been implicated in bone destruction. The objective of this study is to compare circulating levels of DKK1 in different groups of patients with disease activity (remission, low, moderate, high activity,) and functionality status...
December 27, 2017: Clinical Rheumatology
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