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Dickkopf AND Wnt

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https://www.readbyqxmd.com/read/28634697/in-psoriatic-arthritis-dkk-1-and-pth-are-lower-than-in-rheumatoid-arthritis-and-healthy-controls
#1
Angelo Fassio, Luca Idolazzi, Ombretta Viapiana, Camilla Benini, Elisabetta Vantaggiato, Francesco Bertoldo, Maurizio Rossini, Davide Gatti
Psoriatic Arthritis (PsA) is characterized by bone erosive damage often associated with exuberant bone formation especially in enthesial sites. Dkk-1 and sclerostin are the main inhibitors of the WNT/β-catenin signaling pathway and play a key role in the regulation of both bone formation and resorption. We performed this study in order to compare the serum levels of the WNT-pathway regulators along with bone turnover markers (BTM) and parathyroid hormone (PTH) between three different groups: one group of female patients affected by PsA, one group of female patients affected by rheumatoid arthritis (RA), and healthy female controls (HC)...
June 20, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28628652/microrna-433-3p-promotes-osteoblast-differentiation-through-targeting-dkk1-expression
#2
Xiaolin Tang, Jiantao Lin, Guanhai Wang, Jianlin Lu
Dickkopf-1 (DKK1) is a powerful antagonist of canonical WNT signaling pathway, and is regarded as a biomarker for osteoporosis. Its expression is highly correlated with bone mass and osteoblasts maturation. In this study, mouse primary bone marrow cells and osteoblast cell lines were used. Luciferase reporter assay and western blotting methods were employed to validate if miRNA-433-3p epigenetically regulated DKK1 translation. Rat bone marrow derived osteoblasts were infected with lentivirus vector in which miR-433-3p was constructed...
2017: PloS One
https://www.readbyqxmd.com/read/28627829/mir-29a-and-messenger-rna-expression-of-bone-turnover-markers-in-canonical-wnt-pathway-in-patients-with-ankylosing-spondylitis
#3
Jinxian Huang, Guoxiang Song, Zhihua Yin, Zhongchao Fu, Zhizhong Ye
BACKGROUND: Recent studies showed that the canonical Wnt pathway and miR-29a play important roles in the pathogenesis of bone formation. We studied the levels of miR-29a and messenger RNA (mRNA) of bone turnover markers in the canonical Wnt pathway in ankylosing spondylitis (AS). METHODS: The levels of miR-29a and mRNA of bone turnover markers in canonical Wnt pathway from peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction in 38 patients with AS and 32 healthy controls...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28607150/wnt3a-induces-the-expression-of-acetylcholinesterase-during-osteoblast-differentiation-via-the-runx2-transcription-factor
#4
Miranda L Xu, Cathy W C Bi, Etta Y L Liu, Tina T X Dong, Karl W K Tsim
Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, nonneuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28587752/dickkopf-1-inhibits-wnt3a-induced-migration-and-epithelial-mesenchymal-transition-of-human-lens-epithelial-cells
#5
Tingting Liu, Limin Zhang, Yanyan Wang, Haitao Zhang, Lin Li, Xiuli Bao
Posterior capsular opacification (PCO) is a major post-operative complication of cataract surgery. Epithelial-mesenchymal transition (EMT) contributes to PCO. We previously indicated that Wnt3a induces the EMT of human lens epithelial cells (LECs) and plays an important role in the development of PCO. The present study aimed to test the potential effect of Dickkopf-1 (Dkk1) on Wnt3a-induced cell migration and the EMT of LECs and to explore possible cellular mechanisms. The secretion of Dkk1 was reduced in the rabbit PCO model, and Dkk1 injected into the eyes post-surgical manipulation prevented PCO formation...
June 3, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28575156/consequences-of-endogenous-and-exogenous-wnt-signaling-for-development-in-the-preimplantation-bovine-embryo%C3%A2
#6
Paula Tribulo, Beatriz Caetano da Silva Leão, Khoboso C Lehloenya, Gisele Zoccal Mingoti, Peter J Hansen
Although WNT signaling regulates several developmental processes, its specific role during preimplantation development remains unclear. The present aim was to evaluate the consequences of activation and inhibition of β-catenin (CTNNB1) dependent and -independent WNT signaling in the bovine preimplantation embryo. Activation of CTNNB1 mediated WNT signaling by the agonist 2-amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine (AMBMP) and a glycogen synthase kinase 3 (GSK3) inhibitor reduced development to the blastocyst stage...
May 30, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28574171/rationale-for-targeting-the-wnt-signaling-modulator-dkk1-for-oncology
#7
REVIEW
Michael H Kagey, Xi He
Wnt signaling is a fundamental pathway involved in embryonic development and adult tissue homeostasis. Mutations in the pathway frequently lead to developmental defects and cancer. As such, therapeutic intervention of this pathway has generated tremendous interest. Dickkopf-1 (DKK1) is a secreted inhibitor of β-catenin dependent Wnt signaling and was originally characterized as a tumor suppressor based on the prevailing view that Wnt signaling promotes cancer pathogenesis. However, DKK1 appears to increase tumor growth and metastasis in pre-clinical models and its elevated expression correlates with a poor prognosis in a range of cancers, indicating that DKK1 has more complex cellular and biological functions than originally appreciated...
June 2, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28556921/membrane-bound-dickkopf-1-in-foxp3-regulatory-t-cells-suppresses-t-cell-mediated-autoimmune-colitis
#8
Wook-Jin Chae, Jong-Hyun Park, Octavian Henegariu, Saliha Yilmaz, Liming Hao, Alfred L M Bothwell
Induction of tolerance is a key mechanism to maintain or to restore immunological homeostasis. Here we show that Foxp3(+) regulatory T cells (Treg cells) utilize Dickkopf-1 (DKK-1) to regulate T cell-mediated tolerance in the T cell-mediated autoimmune colitis model. Treg cells from DKK-1 hypomorphic doubleridge mice failed to control CD4(+) T cell proliferation, resulting in CD4 T-cell-mediated autoimmune colitis. Thymic-derived Treg cells showed a robust expression of DKK-1 but not in naïve or effector CD4 T cells...
May 30, 2017: Immunology
https://www.readbyqxmd.com/read/28551822/glucocorticoid-therapy-causes-contradictory-changes-of-serum-wnt-signaling-related-molecules-in-systemic-autoimmune-diseases
#9
Mai Kawazoe, Kaichi Kaneko, Kotaro Shikano, Natsuko Kusunoki, Toshihiro Nanki, Shinichi Kawai
The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4 weeks after its initiation...
May 27, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28549605/wnt3a-and-the-induction-of-the-osteogenic-differentiation-in-adipose-tissue-derived-mesenchymal-stem-cells
#10
C Morsczeck, A Reck, T E Reichert
Adipose tissue derived stem cells (ASCs) can easily be isolated, but the osteogenic differentiation potential is limited. To improve this differentiation potential, more investigations are required about signaling proteins for the induction of the osteogenic differentiation. This study focused on the WNT3A protein, because little is known about the canonical WNT signaling pathway and the osteogenic differentiation of ASCs. The alkaline phosphatase (ALP) activity was measured for the evaluation of the osteogenic differentiation...
May 12, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28530511/wnt-signaling-related-osteokines-and-transforming-growth-factors-before-and-after-a-single-bout-of-plyometric-exercise-in-child-and-adolescent-females
#11
Jennifer Dekker, Katlynne Nelson, Nigel Kurgan, Bareket Falk, Andrea Josse, Panagiota Klentrou
This study examined resting levels of catabolic and anabolic osteokines related to Wnt signaling and their responses to a single bout of plyometric exercise in child and adolescent females. Fourteen pre-menarcheal girls (10.5 ± 1.8 years old) and 12 post-menarcheal adolescent girls (15.0 ± 1.0 years old) performed a plyometric exercise trial. One resting and three post-exercise blood samples (5 min, 1h, 24h post-exercise) were analysed for sclerostin (SOST), dickkopf-1 (DKK-1), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-β ligand (RANKL) and transforming growth factors (TGF-β1, TGF-β2 and TGF-β3)...
May 22, 2017: Pediatric Exercise Science
https://www.readbyqxmd.com/read/28526959/adjuvant-tamoxifen-but-not-aromatase-inhibitor-therapy-decreases-serum-levels-of-the-wnt-inhibitor-dickkopf-1-while-not-affecting-sclerostin-in-breast-cancer-patients
#12
Andy Göbel, Jan D Kuhlmann, Theresa Link, Pauline Wimberger, Andrew J Browne, Martina Rauner, Lorenz C Hofbauer, Tilman D Rachner
PURPOSE: Endocrine therapies, including tamoxifen or aromatase inhibitors, are indispensable for the treatment of patients with estrogen receptor (ER)- and/or progesterone-positive breast cancer. Whereas tamoxifen displays partial ER agonistic effects in bone, aromatase inhibitors increase bone resorption and fracture risk. The Wnt inhibitors dickkopf-1 (DKK-1) and sclerostin negatively impact bone formation and are considered targets for the treatment of bone disorders. However, the effect of endocrine therapies on serum DKK-1 and sclerostin levels in patients with primary breast cancer remains elusive...
May 19, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28514532/the-dickkopf1-ckap4-axis-creates-a-novel-signaling-pathway-and-may-represent-a-molecular-target-for-cancer-therapy
#13
REVIEW
Akira Kikuchi, Katsumi Fumoto, Hirokazu Kimura
Dickkopf 1 (DKK1) is a secretory protein and antagonizes oncogenic Wnt signaling by binding to the Wnt co-receptor low-density lipoprotein receptor-related proteins 6 (LRP6). DKK1 is also suggested to regulate its own signaling to associate with tumor aggressiveness. However, the underlying mechanism by which DKK1 promotes cancer cell proliferation has remained to be clarified for a long time. It has been recently found that cytoskeleton-associated protein 4 (CKAP4), which was originally reported as an endoplasmic reticulum membrane protein, acts as a novel DKK1 receptor...
May 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28501564/wntless-promotes-bladder-cancer-growth-and-acts-synergistically-as-a-molecular-target-in-combination-with-cisplatin
#14
Sebastian C Schmid, Anuja Sathe, Ferdinand Guerth, Anna-Katharina Seitz, Matthias M Heck, Tobias Maurer, Sarah M Schwarzenböck, Bernd J Krause, Wolfgang A Schulz, Robert Stoehr, Jürgen E Gschwend, Margitta Retz, Roman Nawroth
PURPOSE: To analyze the contribution of Wnt signaling pathway to bladder cancer growth in order to identify suitable target molecules for therapy. MATERIAL AND METHODS: Expression of Wnt 2/4/7, LRP5/6, TCF1/2/4, LEF-1, and β-actin was detected by reverse transcription polymerase chain reaction in a panel of 9 and for Wntless (WLS) in 17 bladder cancer cell lines. Protein expression of WLS was detected in 6 cell lines. Wnt/β-catenin activity was analyzed using the TOPflash/FOPflash luciferase reporter assay...
May 10, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28493902/circulating-levels-of-sclerostin-but-not-dkk1-associate-with-laboratory-parameters-of-ckd-mbd
#15
Geert J Behets, Liesbeth Viaene, Björn Meijers, Frank Blocki, Vincent M Brandenburg, Anja Verhulst, Patrick C D'Haese, Pieter Evenepoel
INTRODUCTION: Mounting evidence indicates that a disturbed Wnt-β-catenin signaling may be involved in the pathogenesis of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD). Data on the impact of CKD on circulating levels of the Wnt antagonists sclerostin and Dickkopf related protein 1 (DKK1) and the relationship with laboratory parameters of CKD-MBD are incomplete. METHODS: We analyzed serum sclerostin and DKK1 in 308 patients across the stages of chronic kidney disease (kDOQI stage 1-2 n = 41; CKD stage 3 n = 54; CKD stage 4-5 n = 54; hemodialysis n = 100; peritoneal dialysis n = 59) as well as in 49 healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28492360/resveratrol-inhibits-periodontitis-related-bone-loss-in-rats-submitted-to-cigarette-smoke-inhalation
#16
Fernanda V Ribeiro, Danilo S Pino, Felipe C Franck, Bruno B Benatti, Howard Tenenbaum, Dip Perio, John E Davies, Suzana P Pimentel, Renato C Casarin, Fabiano R Cirano, Marcio Z Casati
BACKGROUND: Alternative therapeutic approaches have been explored in order to modulate the host's response to periodontal disease. The knowledge of new strategies to treat periodontitis is particularly relevant in patients presenting augmented risk to periodontitis, as smokers. The aim of this study was to investigate the impact of Resveratrol (RESV) on the progression of experimental periodontitis (EP) in the presence of cigarette smoke inhalation (CSI). METHODS: Rats were assigned to: CSI+RESV(n=20); CSI+placebo(n=20); Non-CSI(n=20)...
May 11, 2017: Journal of Periodontology
https://www.readbyqxmd.com/read/28470144/dkk3-overexpression-increases-malignant-properties-of-head-and-neck-squamous-cell-carcinoma-cells
#17
Naoki Katase, Shin-Ichiro Nishimatsu, Akira Yamauchi, Masahiro Yamamura, Kumiko Terada, Masumi Itadani, Naoko Okada, Nur Mohammad Monsur Hassan, Hitoshi Nagatsuka, Tohru Ikeda, Tsutomu Nohno, Shuichi Fujita
DKK3, a member of dickkopf WNT signaling pathway inhibitor family, is believed to be a tumor suppressor, because of itsreduced expression in cancer cells. However, our previous studies have revealed that DKK3 expression is predominantly observed in head and neck, and oral squamous cell carcinoma (HNSCC/OSCC). Interestingly, HNSCC/OSCC patients with DKK3 expression showed high metastasis rate and poorer survival, and siRNA-mediated knockdown of DKK3 in HNSCC-derived cancer cell lines resulted in reduced cellular migration and invasion...
May 4, 2017: Oncology Research
https://www.readbyqxmd.com/read/28467796/dickkopf-related-protein-2-induces-g0-g1-arrest-and-apoptosis-through-suppressing-wnt-%C3%AE-catenin-signaling-and-is-frequently-methylated-in-breast-cancer
#18
Junhao Mu, Tianli Hui, Bianfei Shao, Lili Li, Zhenfang Du, Li Lu, Lin Ye, Shuman Li, Qianqian Li, Qian Xiao, Zhu Qiu, Yan Zhang, Jiangxia Fan, Guosheng Ren, Qian Tao, Tingxiu Xiang
Dickkopf-related protein 2 (DKK2) is one of the antagonists of Wnt/β-catenin signaling, with its downregulation reported in multiple cancers. However, how DKK2 contributes to breast tumorigenesis remains unclear. We examined its expression and promoter methylation in 10 breast tumor cell lines, 98 primary tumors, and 21 normal breast tissues. Compared with normal tissues, DKK2 was frequently silenced in breast cell lines (7/8). DKK2 promoter methylation was detected in 77.8% of cell lines and 86.7% of breast tumors; while rarely detected in normal breast tissues (19%), indicating common DKK2 methylation in breast cancer...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28455497/decreased-circulating-levels-of-dickkopf-1-in-patients-with-exudative-age-related-macular-degeneration
#19
Fangfang Qiu, Zhen Liu, Yueping Zhou, Jia He, Songjian Gong, Xue Bai, Yingxia Zeng, Zuguo Liu, Jian-Xing Ma
Aberrant activation of the Wnt/β-catenin signaling pathway plays a pathogenic role in retinal inflammation and neovascularization. Here, we investigated whether circulating levels of Dickkopf-1 (DKK-1), a specific inhibitor of this pathway, are altered in patients with exudative age-related macular degeneration (AMD). Plasma was obtained from 128 patients with exudative AMD, 46 patients with atrophic AMD and 111 healthy controls. DKK-1 levels in plasma were measured using ELISA, and data analyzed with one-way ANOVA, logistic regression analysis and receiver-operating characteristic analysis (ROC)...
April 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28451870/association-between-serum-and-synovial-fluid-dickkopf-1-levels-with-radiographic-severity-in-primary-knee-osteoarthritis-patients
#20
Thomas Theologis, Nikolaos Efstathopoulos, Vasileios Nikolaou, Ioannis Charikopoulos, Ioannis Papapavlos, Panayiotis Kokkoris, Athanasios Papatheodorou, Narjes Nasiri-Ansari, Eva Kassi
Primary knee osteoarthritis (OA) contributes to disability among middle-aged and elderly people. Dickkopf-1 (Dkk-1) and sclerostin are inhibitors of Wnt/β-catenin signaling pathway implicated in regulation of cartilage homeostasis and bone formation, respectively. We aim to investigate the association between the serum(s) and synovial fluid (SF) Dkk-1 and sclerostin levels and disease severity in patients with primary knee OA. Forty patients aged 56-87 years with primary knee OA and 20 healthy individuals were recruited...
April 27, 2017: Clinical Rheumatology
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