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Leilei Zhong, Stefano Schivo, Xiaobin Huang, Jeroen Leijten, Marcel Karperien, Janine N Post
Interleukin 1 beta (IL1β) and Wingless-Type MMTV Integration Site Family (WNT) signaling are major players in Osteoarthritis (OA) pathogenesis. Despite having a large functional overlap in OA onset and development, the mechanism of IL1β and WNT crosstalk has remained largely unknown. In this study, we have used a combination of computational modeling and molecular biology to reveal direct or indirect crosstalk between these pathways. Specifically, we revealed a mechanism by which IL1β upregulates WNT signaling via downregulating WNT antagonists, DKK1 and FRZB...
November 22, 2017: International Journal of Molecular Sciences
C Carbone, G Piro, N Gaianigo, F Ligorio, R Santoro, V Merz, F Simionato, C Zecchetto, G Falco, G Conti, P T Kamga, M Krampera, F Di Nicolantonio, L De Franceschi, A Scarpa, G Tortora, D Melisi
BACKGROUND: Solid epidemiological evidences connect obesity with incidence, stage, and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions. METHODS: We studied the role of factors secreted by two adipogenic model systems from primary human Bone Marrow Stromal Cells (hBMSC) in an in vitro experimental cell transformation model system of human pancreatic ductal epithelial (HPDE) cell stably expressing activated KRAS (HPDE/KRAS),RESULTS:We measured a significant induction of EMT and aggressiveness in HPDE and HPDE/KRAS cell lines when cultured with medium conditioned by fully differentiated adipocytes (ADIPO(CM)) if compared with the same cells cultured with medium conditioned by hBMSC (hBMSC(CM)) from two different healthy donors...
November 20, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Jean Cassuto, Agnetha Folestad, Jan Göthlin, Henrik Malchau, Johan Kärrholm
INTRODUCTION: We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. MATERIALS AND METHODS: Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs...
November 10, 2017: Bone
Manru Zhou, Jingkai Wu, Yongjie Yu, Yajun Yang, Jin Li, Liao Cui, Weimin Yao, Yuyu Liu
It is known that long‑term excessive administration of glucocorticoid (GC) results in osteoporosis. The present study aimed to evaluate the protective effects of Polygonum multiflorm (PM) on the bone tissue of rats with GC‑induced osteoporosis (GIO). A total of 90 6‑month‑old female Sprague Dawley rats (weight range, 190‑210 g) were randomly divided into nine groups: Control (normal saline); prednisone (GC; 6 mg·kg‑1·d‑1; Model); GC plus PMR30 (the 30% ethanol eluent fraction of PM) (H) (400 mg·kg‑1·d‑1); GC plus PMR30 (M) (200 mg·kg‑1·d‑1); GC plus PMR30 (L) (100 mg·kg‑1·d‑1); GC plus PMRF (fat‑soluble fraction of PM) (H) (400 mg·kg‑1·d‑1); GC plus PMRF (M) (200 mg·kg‑1·d‑1); GC plus PMRF (L) (100 mg·kg‑1·d‑1); GC plus calcitriol (CAL; 0...
November 7, 2017: Molecular Medicine Reports
Qiwei Yang, Ye Wang, Xiuwu Pan, Jianqing Ye, Sishun Gan, Fajun Qu, Lu Chen, Chuanmin Chu, Yi Gao, Xingang Cui
Recent reports have shown a rapid rise in the incidence of renal cell carcinoma (RCC), and Wnt (Wingless-related integration site) signaling pathway is important in RCC. Frizzled 8 (FZD8) is a member of Frizzled (FZD) receptor family which could activate canonical or non-canonical Wnt/β-catenin pathways. Nevertheless, the role of FZD8 in RCC is poorly investigated. The immunohistochemical analysis showed high expression of FZD8 in RCC tissues compared with peri-tumor tissues. FZD8 knockdown decreased the ability of proliferation and metastasis of RCC cells...
October 3, 2017: Oncotarget
Kacey VanderVorst, Jason Hatakeyama, Anastasia Berg, Hyun Lee, Kermit L Carraway
While the mutational activation of oncogenes drives tumor initiation and growth by promoting cellular transformation and proliferation, increasing evidence suggests that the subsequent re-engagement of largely dormant developmental pathways contributes to cellular phenotypes associated with the malignancy of solid tumors. Genetic studies from a variety of model organisms have defined many of the components that maintain epithelial planar cell polarity (PCP), or cellular polarity in the axis orthogonal to the apical-basal axis...
November 4, 2017: Seminars in Cell & Developmental Biology
Muhammad Abu-Elmagd, Joanna Mulvaney, Grant N Wheeler
Wnt signalling regulates cardiogenesis during specification of heart tissue and the morphogenetic movements necessary to form the linear heart. Wnt11 mediated non-canonical signalling promotes early cardiac development whilst Wnt11-R, which is expressed later, also signals through the non-canonical pathway to promote heart development. It is unclear which Frizzleds mediate these interactions. Frizzled-7 (fzd7) is expressed during gastrulation in the mesodermal cells fated to become heart and then in the primary heart field...
November 3, 2017: Biology Open
Xiang-Jiao Yi, Jin-Cheng Li, Song-Yue Wang, Meng-Yun Yan, Jian Cui, Ling-Peng Pei
This paper was aimed to investigate the effect of Aralia echinocaulis containing serum on expression of β-catenin, Wnt-1, Frizzed-2, TCF and Axin in Wnt/β-catenin signaling pathway of primary osteoblasts. SD healthy female rats (n=80) were used to make A. echinocaulis containing serum by gastric perfusion for seven days with distilled water, A. echinocaulis decoction high dosage, middle dosage, and low dosage. In vitro, primary osteoblasts were cultured and identified. The third generation primary osteoblasts were taken and cultured for 48 h, then cells were treated with the different drug serums for 10 days and calcified nodules were counted by alizarin red staining...
July 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Mitra Soleimani, Nazem Ghasemi
BACKGROUND: Stem cell-based therapy is a novel strategy for the treatment of neurodegenerative diseases. The transplantation of fully differentiated cells instead of stem cells in order to decrease serious adverse complications of stem cell therapy is a new idea. In this study, the effect of lithium chloride on dopaminergic differentiation of human immortalized RenVm cells was investigated in order to access a population of fully differentiated cells for transplantation in Parkinson disease...
October 2017: Avicenna Journal of Medical Biotechnology
S-J Zhao, Y-Q Jiang, N-W Xu, Q Li, Q Zhang, S-Y Wang, J Li, Y-H Wang, Y-L Zhang, S-H Jiang, Y-J Wang, Y-J Huang, X-X Zhang, G-A Tian, C-C Zhang, Y-Y Lv, M Dai, F Liu, R Zhang, D Zhou, Z-G Zhang
Metastasis significantly reduces the survival rate of osteosarcoma (OS) patients. Therefore, identification of novel targets remains extremely important to prevent metastasis and treat OS. In this report, we show that SPARCL1 is downregulated in OS by epigenetic methylation of promoter DNA. In vitro and in vivo experiments revealed that SPARCL1 inhibits OS metastasis. We further demonstrated that SPARCL1-activated WNT/β-catenin signaling by physical interaction with various frizzled receptors and lipoprotein receptor-related protein 5/6, leading to WNT-receptor complex stabilization...
October 30, 2017: Oncogene
Natalie Diepenhorst, Patricia Rueda, Anna E Cook, Philippe Pastoureau, Massimo Sabatini, Christopher J Langmead
Osteoporosis is a progressive bone disorder characterised by imbalance between bone building (anabolism) and resorption (catabolism). Most therapeutics target inhibition of osteoclast-mediated bone resorption, but more recent attention in early drug discovery has focussed on anabolic targets in osteoblasts or their precursors. Two marketed agents that display anabolic properties, strontium ranelate and teriparatide, mediate their actions via the G protein-coupled calcium-sensing and parathyroid hormone-1 receptors, respectively...
October 25, 2017: Pharmacology & Therapeutics
Elise Sandsmark, Maria K Andersen, Anna M Bofin, Helena Bertilsson, Finn Drabløs, Tone F Bathen, Morten B Rye, May-Britt Tessem
Increased knowledge of the molecular differences between indolent and aggressive prostate cancer is needed for improved risk stratification and treatment selection. Secreted frizzled-related protein 4 (SFRP4) is a modulator of the cancer-associated Wnt pathway, and previously suggested as a potential marker for prostate cancer aggressiveness. In this study, we investigated and validated the association between SFRP4 gene expression and aggressiveness in nine independent cohorts (n = 2157). By differential expression and combined meta-analysis of all cohorts, we detected significantly higher SFRP4 expression in cancer compared with normal samples, and in high (3-5) compared with low (1-2) Grade Group samples...
October 27, 2017: Scientific Reports
Julie L Frey, Soohyun P Kim, Zhu Li, Michael J Wolfgang, Ryan C Riddle
Wnt-initiated signaling through a frizzled receptor and the low-density lipoprotein related receptor-5 (Lrp5) co-receptor instructs key anabolic events during skeletal development, homeostasis, and repair. Recent studies indicate that Wnt signaling also regulates the intermediary metabolism of osteoblastic cells, inducing glucose consumption in osteoprogenitors and fatty acid utilization in mature osteoblasts. In this study, we examined the role of the canonical Wnt-signaling target, β-catenin, in the control of osteoblast metabolism...
October 25, 2017: Endocrinology
S-L Xie, S Fan, S-Y Zhang, W-X Chen, Q-X Li, G-K Pan, H-Q Zhang, W-W Wang, B Weng, Z Zhang, J-S Li, Z-Y Lin
A sub-population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumour relapse and metastasis. In this study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin-resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin-resistant TSCC cells, which displayed CSC-like properties and exhibited EMT...
October 26, 2017: International Journal of Cancer. Journal International du Cancer
Qing-Qing Fan, Fei-Long Meng, Ran Fang, Gao-Peng Li, Xiao-Li Zhao
Wnt signaling pathway plays important roles in the development and homeostasis of multicellular organisms. Through their bindings with the Frizzled receptors, the Wnt ligands regulate a wide range of developmental processes, such as axis patterning, cell division, and cell fate specification. Wnt signaling plays vital roles in the development of inner ear of the mouse. In the early stages of inner ear development, Wnt signaling specifies the size of the placode and the formation of the otic vesicle. In later stages, Wnt signaling mediates hair cell specification and orients the stereociliary bundles in a uniform direction...
October 20, 2017: Yi Chuan, Hereditas
Jun Zeng, Jiongyu Hu, Yu Lian, Youzhao Jiang, Bing Chen
Secreted frizzled-related protein 5 (SFRP5) is a newly identified adipokine. SFRP5 expression increases during the differentiation and maturation of adipocytes, but the factors regulating SFRP5 expression during this process remain unclear. This study showed that peroxisome proliferator-activated receptor γ (PPARγ) adenovirus transfection could enhance the SFRP5 expression of 3T3-L1 adipocytes. Three potential binding sites of PPARγ in the SFRP5 promoter domain were found by bioinformatics analysis. Luciferase reporter gene assay demonstrated that PPARγ regulated the activity of the SFRP5 promoter through cis-acting elements at -2,284--1,500bp...
October 21, 2017: Gene
Sami Hamdoun, Edmond Fleischer, Annette Klinger, Thomas Efferth
Multidrug resistance (MDR) represents a serious problem in cancer treatment. One strategy to overcome this obstacle is to identify agents that are selectively lethal to MDR cells. The aim of this study was to discover novel compounds against MDR leukemia and to determine the molecular mechanisms behind collateral sensitivity. A library of 1162 compounds was tested against parental, drug-sensitive CCRF-CEM cells using the resazurin assay. At total of 302 compounds showed reasonable activity (less than 50% cell viability)...
October 20, 2017: Biochemical Pharmacology
Abdulhalim Senyigit, Omur Tabak, Timur Orhanoglu, Aytac Karadag, Serdal Ugurlu, Hafize Uzun, Dildar Konukoglu
PURPOSE: Hyperglycemia is the major risk factor for microvascular complications in type 2 diabetes mellitus (T2DM) patients. This randomized controlled clinical trial aimed to investigate T2DM patients with microvascular complications with regard to possible relations among serum clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4) activities. METHODS: Subject groups were defined as follows: T2DM without complications (n=25, F/M=9/16, age 53...
October 19, 2017: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
Qingwei Ji, Jianwei Zhang, Yu Du, Enjun Zhu, Zhijian Wang, Bin Que, Huangtai Miao, Shutian Shi, Xiuchuan Qin, Yingxin Zhao, Yujie Zhou, Fangjun Huang, Shaoping Nie
BACKGROUND: Previous studies have demonstrated that secreted frizzled-related protein 4 (SFRP4) is associated with impaired glucose and triglyceride metabolism in patients with stable coronary artery disease. In the present study, we investigated human epicardial adipose tissue (EAT)-derived and circulating SFRP4 levels in patients with coronary artery disease (CAD). METHODS: Plasma samples and adipose biopsies from EAT and subcutaneous adipose tissue (SAT) were collected from patients with CAD (n = 40) and without CAD (non-CAD, n = 30) during elective cardiac surgery...
October 16, 2017: Cardiovascular Diabetology
Ting-Ting Cao, Di Xiang, Bei-Lei Liu, Tu-Xiong Huang, Bin-Bin Tan, Chui-Mian Zeng, Zhong-Yuan Wang, Xiao-Yan Ming, Li-Yi Zhang, Guangyi Jin, Feng Li, Jian-Lin Wu, Xin-Yuan Guan, Desheng Lu, Li Fu
Frizzled (FZD) proteins are receptors for secreted WNT proteins and play a critical role in the malignant progression of various cancers. However, the role of human FZD family members in esophageal squamous cell carcinoma (ESCC) was rarely investigated. In this study, we found that the FZD7 gene was the most commonly up-regulated FZD member in ESCC cell lines compared with other FZDs. TMA studies further validated that FZD7 protein was up-regulated in 165 of 252 (65.5%) informative ESCC patients and significantly correlated with poor overall survival (P=0...
September 12, 2017: Oncotarget
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