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Dickkopf AND Wnt

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https://www.readbyqxmd.com/read/29774401/high-levels-of-serum-sclerostin-and-dkk1-in-a-case-of-klippel-tr%C3%A3-naunay-syndrome
#1
P Muto, A Lo Gullo, G Mandraffino, S Loddo, M Atteritano
Klippel-Trénaunay syndrome (KTS) is described as a complex syndrome characterized by various combinations of capillary, venous, and lymphatic malformations associated with bone and soft tissue hypertrophy. We report a case of a 67-year-old postmenopausal Caucasian women with KTS that shows elevated levels of sclerostin and Dickkopf-related protein 1 (DKK1). Dual-energy X-ray absorptiometry (DXA) BMD T-scores at lumbar spine and femur were normal. Serum calcium and phosphorus levels were consistently normal, 25-hydroxyvitamin D (25OHD) < 30 ng/mL, and normal parathyroid hormone (PTH)...
May 17, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29772510/dkk1-and-kremen-expression-predicts-the-osteoblastic-response-to-bone-metastasis
#2
Katrina L Clines, Gregory A Clines
Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis...
May 14, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29763912/-a-succinate-ether-derivative-of-tocotrienol-enhances-dickkopf-1-gene-expression-through-epigenetic-alterations-in-malignant-mesothelioma-cells
#3
Ayami Sato, Haruka Ueno, Momoka Fusegi, Saki Kaneko, Kakeru Kohno, Nantiga Virgona, Akira Ando, Yuko Sekine, Tomohiro Yano
BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1)...
May 15, 2018: Pharmacology
https://www.readbyqxmd.com/read/29749516/downregulation-of-n%C3%A2-myc-inhibits-neuroblastoma-cell-growth-via-the-wnt-%C3%AE-%C3%A2-catenin-signaling-pathway
#4
Yingge Wang, Shan Gao, Weiguang Wang, Yuting Xia, Jingyan Liang
Neuroblastoma, one of the most common types of cancer in childhood, is commonly treated with surgery, radiation and chemotherapy. However, prognosis and survival remain poor for children with high‑risk neuroblastoma. Therefore, the identification of novel, effective therapeutic targets is necessary. N‑Myc, a proto‑oncogene protein encoded by the v‑myc avial myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) gene, is associated with tumorigenesis. In the present study, the effect of N‑Myc silencing on MYCN‑amplified CHP134 and BE‑2C neuroblastoma cells was evaluated, and the underlying molecular mechanism was investigated...
May 3, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29734465/postnatal-skeletal-deletion-of-dickkopf-1-increases-bone-formation-and-bone-volume-in-male-and-female-mice-despite-increased-sclerostin-expression
#5
Juliane Colditz, Sylvia Thiele, Ulrike Baschant, Christof Niehrs, Lynda F Bonewald, Lorenz C Hofbauer, Martina Rauner
The Wnt antagonist Dickkopf-1 (Dkk1) is a negative regulator of osteoblast function and bone mass. However, due to the lack of appropriate models, many aspects of its role in the regulation of postnatal bone turnover and its cellular source have remained unknown. In this study, we deleted Dkk1 postnatally and in different cell types using various Cre-drivers (Rosa26-ERT2-Cre, Osx-cre,Dmp1-Cre) and assessed to which extent cells of the osteoblastic lineage contribute to the effects of Dkk1 on bone turnover and homeostasis...
May 7, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29731902/identification-of-candidate-genes-associated-with-tubal-origin-of-high-grade-serous-ovarian-cancer
#6
Li Xiang, Guohua Rong, Jing Zhao, Zhenyan Wang, Fengfeng Shi
Evidence indicates that high-grade serous ovarian carcinoma arises from the fallopian tube, rather than ovarian surface epithelium. This is termed the 'tubal origin' theory. The aim of the present study was to compare the immunophenotype and gene expression profiling among high-grade serous ovarian carcinoma (HGSOC), fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) based on tubal origin theory, and identify the differential genes associated with ovarian carcinogenesis. A total of 61 cases of fresh tissue samples including 21 cases of HGSOC, 20 cases of OSE, and 20 cases of FTE were obtained following surgical resection...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29726981/dickkopf-3-in-aberrant-endothelial-secretome-triggers-renal-fibroblast-activation-and-endothelial-mesenchymal-transition
#7
Mark Lipphardt, Hassan Dihazi, Noo Li Jeon, Sina Dadafarin, Brian B Ratliff, David W Rowe, Gerhard A Müller, Michael S Goligorsky
Background: Our laboratory has previously demonstrated that Sirt1endo-/- mice show endothelial dysfunction and exaggerated renal fibrosis, whereas mice with silenced endothelial transforming growth factor beta (TGF-β) signaling are resistant to fibrogenic signals. Considering the fact that the only difference between these mutant mice is confined to the vascular endothelium, this indicates that secreted substances contribute to these contrasting responses. Methods: We performed an unbiased proteomic analysis of the secretome of renal microvascular endothelial cells (RMVECs) isolated from these two mutants...
May 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29725706/abaloparatide-exerts-bone-anabolic-effects-with-less-stimulation-of-bone-resorption-related-factors-a-comparison-with-teriparatide
#8
Akito Makino, Hideko Takagi, Yoshimasa Takahashi, Naoki Hase, Hiroyuki Sugiyama, Kei Yamana, Tsunefumi Kobayashi
Abaloparatide (ABL) is a novel synthetic peptide analog of parathyroid hormone-related protein. In previous reports, intermittent ABL administration showed robust bone mineral density (BMD) increase and reduced the incidence of fractures in patients with osteoporosis, while its calcemic effect was reduced, as compared with teriparatide (TPTD), a parathyroid hormone N-terminal fragment. The present study aimed to elucidate the effects of ABL on bone anabolism and bone turnover as compared with TPTD. In ovariectomized (OVX) rats, ABL increased the bone strength and BMD of lumbar spine by intermittent administration similar to TPTD...
May 3, 2018: Calcified Tissue International
https://www.readbyqxmd.com/read/29720122/prognostic-value-of-dickkopf-1-and-%C3%A3-catenin-expression-in-advanced-gastric-cancer
#9
Soon Auck Hong, Su Hyun Yoo, Han Hong Lee, Der Sheng Sun, Hye Sung Won, Okran Kim, Yoon Ho Ko
BACKGROUND: Dickkopf-1 (DKK1) is a Wnt/ß-catenin pathway antagonist related to gastric cancer (GC) carcinogenesis. However, the prognostic role of combined DKK1 and ß-catenin expression in advanced GC (AGC) is not clear. METHODS: In total, 158 patients with AGC who underwent gastric resection were enrolled in this study. DKK1 and ß-catenin expression was evaluated in whole tumor sections by immunohistochemistry. RESULTS: DKK1 expression was high in 73 (46...
May 2, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29715368/cross-inhibition-of-norrin-and-tgf-%C3%AE-signaling-modulates-development-of-retinal-and-choroidal-vasculature
#10
Roswitha Seitz, Gregor Weber, Sebastian Albrecht, Rudolf Fuchshofer, Ernst R Tamm, Andreas Ohlmann
Purpose: Norrin is essential for the formation of the retinal vasculature during development and promotes its repair after damage via activation of Wnt/β-catenin signaling. Since retinal TGF-β signaling has essentially opposite effects on the retinal vasculature we investigated if and how Norrin inhibits TGF-β signaling, and vice versa. Methods: Eyes from transgenic mice with an overexpression of Norrin (βB1-Norrin) and/or active TGF-β (βB1-TGF-β1) in the lens were generated and analyzed by light microscopy, immunohistochemistry, and TUNEL...
May 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29704238/microrna-3064-3p-regulates-the-differentiation-of-cementoblasts-through-targeting-dkk1
#11
C Wang, H Liao, H Sun, Y Zhang, Z Cao
BACKGROUND AND OBJECTIVE: MicroRNAs (miRNAs) are short, noncoding RNAs that interfere with translation of target mRNAs and thereby play a pivotal role in a variety of biological processes. Cementoblasts are the cells that build up cementum. They share a similar gene expression pattern with osteoblasts. Recent studies have suggested that miRNAs are able to control osteoblast-mediated bone formation. However, the effects of miRNA on cementoblast differentiation still remain unsolved. Herein, we wanted to elucidate the role of miR-3064-3p in cementoblast differentiation...
April 27, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29694926/gh-prevents-adipogenic-differentiation-of-mesenchymal-stromal-stem-cells-derived-from-human-trabecular-bone-via-canonical-wnt-signaling
#12
Simona Bolamperti, Michela Signo, Alice Spinello, GianLuigi Moro, Gianfranco Fraschini, Francesca Guidobono, Alessandro Rubinacci, Isabella Villa
The imbalance between osteogenesis and adipogenesis, which naturally accompanies bone marrow senescence, may contribute to the development of bone-associated diseases, like osteoporosis. In the present study, using primary human mesenchymal stromal cells (hMSCs) isolated from trabecular bone, we assessed the possible effect of GH on hMSC differentiation potential into adipocytes. GH (5 ng/ml) significantly inhibited the lipid accumulation in hMSCs cultured for 14 days in lipogenic medium. GH decreased the expression of the adipogenic genes, CCAAT/enhancer-binding protein alpha (C/EBPα) and adiponectin (ADN) as well as the expression of two lipogenesis-related enzymes, lipoprotein lipase (LPL) and acethylCoA carboxylase (ACACA)...
April 22, 2018: Bone
https://www.readbyqxmd.com/read/29693006/baicalein-accelerates-tendon-bone-healing-via-activation-of-wnt-%C3%AE-catenin-signaling-pathway-in-rats
#13
Xinggui Tian, Huaji Jiang, Yuhui Chen, Xiang Ao, Chuan Chen, Wentao Zhang, Feilin He, Xiaoqing Liao, Xiaocheng Jiang, Tao Li, Zhongmin Zhang, Xintao Zhang
Background: Tendon-bone healing is a reconstructive procedure which requires a tendon graft healing to a bone tunnel or to the surface of bone after the junction injury between tendon, ligament, and bone. The surgical reattachment of tendon to bone often fails due to regeneration failure of the specialized tendon-bone junction. Materials and Methods: An extra-articular tendon-bone healing rat model was established to discuss the effect of the baicalein 10 mg/(kg·d) in accelerating tendon-bone healing progress...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29683771/wnt-signaling-related-osteokines-at-rest-and-following-plyometric-exercise-in-prepubertal-and-early-pubertal-boys-and-girls
#14
Panagiota Klentrou, Kirina Angrish, Nafisa Awadia, Nigel Kurgan, Rozalia Kouvelioti, Bareket Falk
PURPOSE: This study examined osteokines related to Wnt signaling at rest and in response to plyometric exercise in 12 boys [10.2 (0.4) y] and 12 girls [10.5 (0.4) y]. METHODS: One resting (preexercise) and 3 postexercise (5 min, 1 h, and 24 h) blood samples were analyzed for sclerostin, dickkopf-related protein 1 (DKK-1), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-β ligand (RANKL). RESULTS: Girls had higher resting sclerostin than boys [187...
April 23, 2018: Pediatric Exercise Science
https://www.readbyqxmd.com/read/29674765/clinical-and-functional-significance-of-intracellular-and-extracellular-microrna-25-3p-in-osteosarcoma
#15
Aki Yoshida, Tomohiro Fujiwara, Koji Uotani, Takuya Morita, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki
Although there is considerable evidence indicating that the dysregulation of microRNAs (miRNAs) in malignant tumors plays a role in tumor development, the overall function of miRNAs and their clinicopathological significance are not well understood. In this retrospective analysis of 45 biopsy specimens from osteosarcoma (OS) patients, we investigated the functional and clinical significance of miR-25-3p in OS, which we previously identified as a highly expressed miRNA in OS patients' serum. We observed that miR-25-3p dysregulation in human OS tissues was negatively correlated with the clinical prognosis, whereas the expression level of its target gene, Dickkopf WNT Signaling Pathway Inhibitor 3 (DKK3), was positively correlated with the clinical prognosis...
April 2018: Acta Medica Okayama
https://www.readbyqxmd.com/read/29673070/mycn-is-a-novel-oncogenic-target-in-adult-b-all-that-activates-the-wnt-%C3%AE-catenin-pathway-by-suppressing-dkk3
#16
Desheng Kong, Linlin Zhao, Lili Sun, Shengjin Fan, Huibo Li, Yanqiu Zhao, Zhibo Guo, Leilei Lin, Lin Cui, Ke Wang, Wenjia Chen, Yihui Zhang, Jin Zhou, Yinghua Li
Dickkopf-3 (DKK3) is frequently down-regulated by promoter hypermethylation and is closely associated with a poor prognosis in many cancers. Our previous studies have shown that miR-708 down-regulates DKK3 at the post-transcriptional level in B-ALL. However, whether transcriptional mechanisms lead to DKK3 silencing remains unclear. Here, we analysed the promoter regions of DKK3 by bioinformatics and found binding sites for MYCN. A dual-luciferase reporter gene assay and ChIP experiments revealed that MYCN negatively regulates DKK3 at the transcriptional level in B-ALL cell lines, and using bisulphite sequencing PCR, we affirmed that MYCN has no effect on the methylation of the DKK3 promoter...
April 19, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29665496/the-serum-level-of-dickkopf-1-in-patients-with-rheumatoid-arthritis-a-systematic-review-and-meta-analysis
#17
REVIEW
Yubo Ma, Xu Zhang, Mengmeng Wang, Qing Xia, Jiajia Yang, Meng Wu, Renfang Han, Mengya Chen, Xingxing Hu, Yaping Yuan, Rui Liu, Guangming Jiang, Guixia Pan, Yanfeng Zou, Shengqian Xu, Faming Pan
OBJECTIVE: Dickkopf-1 (DKK-1) is an endogenous inhibitor of canonical Wnt pathway that was implicated in the pathogenesis of rheumatoid arthritis (RA), but the serum levels of DKK-1 in RA were inconsistent among studies. Therefore, we conducted a meta-analysis to systematically evaluate the relationship between serum DKK-1 levels and RA. METHODS: PubMed, Web of Science and Cochrane Library were comprehensively retrieved till 1 January 2018 for pertinent studies...
April 14, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29649633/circulating-wnt-inhibitory-factor-1-levels-are-associated-with-development-of-cardiovascular-disease
#18
Claudia Ress, Mariya Paulweber, Georg Goebel, Karin Willeit, Kerstin Rufinatscha, Anna Strobl, Karin Salzmann, Ludmilla Kedenko, Alexander Tschoner, Gabriele Staudacher, Bernhard Iglseder, Herbert Tilg, Bernhard Paulweber, Susanne Kaser
BACKGROUND AND AIMS: Wnt signaling is involved in atherosclerotic plaque formation directly and indirectly by modulating cardiovascular risk factors. We investigated whether circulating concentrations of Wnt inhibitors are associated with cardiovascular events in subjects with intermediate cardiovascular risk. METHODS: 904 non-diabetic subjects participating in the SAPHIR study were assessed. In the SAPHIR study, middle-aged women without overt atherosclerotic disease at study entry were followed up for 10 years...
March 29, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29643768/mirna-431-prevents-amyloid-%C3%AE-induced-synapse-loss-in-neuronal-cell-culture-model-of-alzheimer-s-disease-by-silencing-kremen1
#19
Sean P Ross, Kelly E Baker, Amanda Fisher, Lee Hoff, Elena S Pak, Alexander K Murashov
Synapse loss is well regarded as the underlying cause for the progressive decline of memory function over the course of Alzheimer's disease (AD) development. Recent observations suggest that the accumulation of the Wnt antagonist Dickkopf-1 (Dkk1) in the AD brain plays a critical role in triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block the Wnt/β-catenin signaling pathway. Here, we show that silencing Krm1 with miR-431 prevents amyloid-β-mediated synapse loss in cortico-hippocampal cultures isolated from triple transgenic 3xTg-AD mice...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29603740/nicotine-inhibits-osteogenic-differentiation-of-human-periodontal-ligament-cells-under-cyclic-tensile-stress-through-canonical-wnt-pathway-and-%C3%AE-7-nicotinic-acetylcholine-receptor
#20
W Yu, B Hu, X Shi, Z Cao, M Ren, Z He, J Lin, H Deng, R Hu
BACKGROUND AND OBJECTIVES: Nicotine, the main psychoactive component of tobacco, affects cell metabolism, proliferation, adhesion and, importantly, the osteogenic differentiation of fibroblasts. Approximately 15% of all orthodontic patients are adults among who one-fifth are smokers. Hence, it is necessary to have insight into the effects of nicotine on the osteogenic differentiation of hPDLCs during orthodontic tooth movement. This study aimed to investigate the effects and mechanisms of nicotine on the osteogenic differentiation of human periodontal ligament cells (hPDLCs) under the application of cyclic tensile stress...
March 30, 2018: Journal of Periodontal Research
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