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https://www.readbyqxmd.com/read/28222408/severe-osteoporosis-with-multiple-spontaneous-vertebral-fractures-in-a-young-male-carrying-triple-polymorphisms-in-the-vitamin-d-receptor-collagen-type-1-and-low-density-lipoprotein-receptor-related-peptide-5-genes
#1
Maria P Yavropoulou, Panagoulia Kollia, Dimitris Chatzidimitriou, Stavroula Samara, Lemonia Skoura, John G Yovos
: Osteoporosis is a common disease with a strong genetic component. Several studies have reported the vitamin D receptor (VDR), collagen type I (COL1A1), and LDL receptor-related protein 5 (LRP5) genes as the most likely candidates. However, most of the studies have been carried out in postmenopausal women and older men and show inconsistent results. CASE PRESENTATION: We report a case of a 26-year old male who presented with severe back pain of acute onset, unrelated to any kind of trauma, and diffuse myalgia...
October 2016: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28158288/mir-375-3p-negatively-regulates-osteogenesis-by-targeting-and-decreasing-the-expression-levels-of-lrp5-and-%C3%AE-catenin
#2
Tianhao Sun, Chen-Tian Li, Lifeng Xiong, Ziyu Ning, Frankie Leung, Songlin Peng, William W Lu
Wnt signaling pathways are essential for bone formation. Previous studies showed that Wnt signaling pathways were regulated by miR-375. Thus, we aim to explore whether miR-375 could affect osteogenesis. In the present study, we investigated the roles of miR-375 and its downstream targets. Firstly, we revealed that miR-375-3p negatively modulated osteogenesis by suppressing positive regulators of osteogenesis and promoting negative regulators of osteogenesis. In addition, the results of TUNEL cell apoptosis assay showed that miR-375-3p induced MC3T3-E1 cell apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#3
Dorra Elhaj Mahmoud, Nadia Sassi, Ghassen Drissi, Maher Barsaoui, Khaled Zitouna, Hela Sahli, Maryam Kallel-Sellami, Lassad Kanoun, Elhem Cheour, Lilia Laadhar
CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28145787/osteoporosis-pseudoglioma-syndrome-report-of-two-cases-and-a-manifesting-carrier
#4
Paolo Maltese, Lucia Ziccardi, Giancarlo Iarossi, Elena Gusson, Leonardo D'Agruma, Giorgio Marchini, Luca Buzzonetti, Annalisa Nicoletti, Sabrina Benedetti, Matteo Bertelli
BACKGROUND: Osteoporosis-pseudoglioma syndrome is a very rare disease mainly characterized by severe eye abnormalities and osteoporosis but also causing a broader range of clinical features. The syndrome is associated with homozygous or compound heterozygous variations in the LRP5 gene. In this report, we describe two children with a severe early-onset form of familial exudative vitreoretinopathy associated with skeletal abnormalities. MATERIALS AND METHODS: Two probands (4 and 7 years of age respectively) and their parents were assessed by genetic analysis and comprehensive ophthalmic examination...
February 1, 2017: Ophthalmic Genetics
https://www.readbyqxmd.com/read/28143772/stearoyl-coa-desaturase-promotes-liver-fibrosis-and-tumor-development-in-mice-via-a-wnt-positive-signaling-loop-by-stabilization-of-low-density-lipoprotein-receptor-related-proteins-5-and-6
#5
Keane K Y Lai, Soo-Mi Kweon, Feng Chi, Edward Hwang, Yasuaki Kabe, Reiichi Higashiyama, Lan Qin, Rui Yan, Raymond P Wu, Naoaki Fujii, Samuel French, Jun Xu, Jian-Ying Wang, Ramanchadran Murali, Lopa Mishra, Ju-Seog Lee, James M Ntambi, Hidekazu Tsukamoto
BACKGROUND & AIMS: Stearoyl-CoA desaturase (SCD) synthesizes monounsaturated fatty acids (MUFAs) and has been associated with development of metabolic syndrome, tumorigenesis, and stem cell characteristics. We investigated whether and how SCD promotes liver fibrosis and tumor development in mice. METHODS: Rodent primary hepatic stellate cells (HSCs), mouse liver tumor-initiating stem cell-like cells (TICs), and human hepatocellular carcinoma (HCC) cell lines were exposed to Wnt signaling inhibitors and changes in gene expression patterns were analyzed...
January 29, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28139941/polymorphism-in-lrp5-rs556442-is-associated-with-higher-tg-levels-in-iranian-children
#6
Nima Montazeri-Najafabady, Mohammad Hossein Dabbaghmanesh, Gholamhossein Ranjbar Omrani, Forough Saki, Marzieh Bakhshayeshkaram
BACKGROUND: Wnt signaling/LRP5 is involved in adipogenesis by down-regulating adipogenic transcription factors. Therefore polymorphisms in components of this pathway may lead to metabolic disorders. AIM: In this study, we tested the impact of LRP5 polymorphism on lipid profile in Iranian children. METHODS: The study population was comprised of 9-18 year old children (125 boys, 137 girls). Total cholesterol (TC), High Density Lipoprotein (HDL), Low-Density Lipoprotein (LDL), Non HDL cholesterol and Triglyceride (TG) levels were checked...
January 31, 2017: Annals of Human Biology
https://www.readbyqxmd.com/read/28122918/nuclear-factor-i-c-reciprocally-regulates-adipocyte-and-osteoblast-differentiation-via-control-of-canonical-wnt-signaling
#7
Jie Zhou, Shan Wang, Qi Qi, Xiaoyue Yang, Endong Zhu, Hairui Yuan, Xuemei Li, Ying Liu, Xiaoxia Li, Baoli Wang
Nuclear factor I-C (NFIC) has recently been identified as an important player in osteogenesis and bone homeostasis in vivo However, the molecular mechanisms involved have yet to be defined. In the current study, Nfic expression was altered in primary marrow stromal cells and established progenitor lines after adipogenic and osteogenic treatment. Overexpression of Nfic in stromal cells ST2, mesenchymal cells C3H10T1/2, and primary marrow stromal cells inhibited adipogenic differentiation, whereas it promoted osteogenic differentiation...
January 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28111184/lrp5-linked-osteoporosis-pseudoglioma-syndrome-mimicking-isolated-microphthalmia
#8
Sezen Guntekin Ergun, Guvem Gumus Akay, Mehmet Ali Ergun, E Ferda Perçin
Microphthalmia is defined as the measurement of the total axial length of the eyeball to be below average of the two standard deviation according to the age. While several genes have been identified so far related to microphthalmia, the genetic etiology of the disease has not been fully understood because of genetic heterogeneity observed in this disease. After exclusion of the genes that had been known to be the cause of microphthalmia, we performed homozygosity mapping and exome sequencing to clarify the genetic etiology of the bilateral microphthalmia in this family...
March 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28072409/alcohol-dose-dependent-dna-methylation-and-expression-in-the-nucleus-accumbens-identifies-coordinated-regulation-of-synaptic-genes
#9
R Cervera-Juanes, L J Wilhelm, B Park, K A Grant, B Ferguson
Alterations in DNA methylation have been associated with alcohol exposure and proposed to contribute to continued alcohol use; however, the molecular mechanisms involved remain obscure. We investigated the escalating effects of alcohol use on DNA methylation, gene expression and predicted neural effects in the nucleus accumbens of rhesus macaques that self-administered 4% alcohol for over 12 months. Using an exploratory approach to identify CpG-rich regions, followed by bisulfite sequencing, the methylation levels of 2...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28067456/type-2-diabetes-mellitus-associated-with-the-interaction-of-lrp5-polymorphism-and-overweight-and-obesity-in-rural-chinese-adults
#10
Zhang Lu, Wang Jinjin, Zhang Ming, Wang Guo'an, Shen Yanxia, Wu Dongting, Wang Chongjian, Li Linlin, Ren Yongcheng, Wang Bingyuan, Zhang Hongyan, Yang Xiangyu, Zhao Yang, Han Chengyi, Zhou Junmei, Pang Chao, Yin Lei, Zhao Jingzhi, Luo Xinping, Hu Dongsheng
BACKGROUND: Low-density lipoprotein receptor-related protein 5 (LRP5) plays an important role in glucose and cholesterol metabolism, so a cohort study was used to evaluate the association of LRP5 variants and incidence of type 2 diabetes mellitus (T2DM) in a rural adult Chinese population. METHODS: A total of 7751 subjects ≥18 years old and without T2DM underwent genotyping at baseline; 6326 subjects (81.62%) were followed-up, with 5511 eligible for this analysis...
January 9, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28063934/morphine-administration-induces-change-in-anxiety-related-behavior-via-wnt-%C3%AE-catenin-signaling
#11
Jiancai Wang, Gang Zhu, Lu Huang, Tiejian Nie, Kai Tao, Yuqian Li, Guodong Gao
Chronic morphine administration is known to decrease anxiety-related behavior, which may lead to morphine-seeking and other social problems. Recent studies have revealed that Wnt/β-catenin signaling plays an important role in anxiety-related behavior. We used HT22 cells, which were derived from primary mouse hippocampal neuronal cultures, to explore the relationship between Wnt signaling and morphine exposure. Many techniques, such as western blot analysis, immunofluorescence and luciferase assays, were utilized...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28059551/wnt-signaling-in-chronic-rhinosinusitis-with-nasal-polyps
#12
Robert Böscke, Eszter K Vladar, Michael Könnecke, Birgit Hüsing, Robert Linke, Ralph Pries, Norbert Reiling, Jeffrey D Axelrod, Jayakar V Nayak, Barbara Wollenberg
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs...
January 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28056548/l-carnitine-contributes-to-enhancement-of-neurogenesis-from-mesenchymal-stem-cells-through-wnt-%C3%AE-catenin-and-pka-pathway
#13
Ezzatollah Fathi, Raheleh Farahzadi, Hojjatollah Nozad Charoudeh
The identification of factors capable of enhancing neurogenesis has great potential for cellular therapies in neurodegenerative diseases. Multiple studies have shown the neuroprotective effects of L-carnitine (LC). This study determined whether neuronal differentiation of rat adipose tissue-derived mesenchymal stem cells (ADSCs) can be activated by LC. In this study, protein kinase A (PKA) and Wnt/β-catenin pathways were detected to show if this activation was due to these pathways. The expression of LC-induced neurogenesis markers in ADSCs was characterized using real-time PCR...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28049091/taspine-derivative-12k-suppressed-a549-cell-migration-through-the-wnt-%C3%AE-catenin-and-ephrinb2-signaling-pathway
#14
Bingling Dai, Yujiao Ma, Tianfeng Yang, Wenjie Wang, Yanmin Zhang
12k, a taspine derivative, has been demonstrated to have the potent anti-tumor activity in lung cancer and colorectal cancer. The study aims to further explore the underlying mechanisms of 12k on A549 cell migration in vitro. Our data demonstrated that 12k negatively regulated Wnt signaling pathway by suppressing the phosphorylation of LRP5/6, and inhibiting the expression and nuclear translocation of β-catenin. 12k was shown to downregulate MMP3 and MMP7 expression which regulated by β-catenin interacts with TCF/LEF in the nucleus, and effectively impaired the related migration protein expression of MMP2 and MMP9 in A549 cells...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28028632/the-rs3736228-polymorphism-in-the-lrp5-gene-is-associated-with-calcaneal-ultrasound-parameter-but-not-with-body-composition-in-a-cohort-of-young-caucasian-adults
#15
María Correa-Rodríguez, Jacqueline Schmidt-RioValle, Blanca Rueda-Medina
The aim of the present study was to investigate the possible influence of low-density lipoprotein receptor-related protein 5 (LRP5) and sclerostin (SOST) genes as genetic factors contributing to calcaneal quantitative ultrasound (QUS) and body composition variables in a population of young Caucasian adults. The study population comprised a total of 575 individuals (mean age 20.41years; SD 2.36) whose bone mass was assessed through QUS to determine broadband ultrasound attenuation (BUA, dB/MHz). Body composition measurements were performed using a body composition analyser...
December 27, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28002565/large-deletions-of-tspan12-cause-familial-exudative-vitreoretinopathy-fevr
#16
Soo Hyun Seo, Man Jin Kim, Sung Wook Park, Jeong Hun Kim, Young Suk Yu, Ji Yun Song, Sung Im Cho, Joo Hyun Ahn, Yeon Hee Oh, Jee-Soo Lee, Seungjun Lee, Moon-Woo Seong, Sung Sup Park, Ji Yeon Kim
Purpose: Familial exudative vitreoretinopathy (FEVR) is a rare, hereditary visual disorder. The gene TSPAN12 is associated with autosomal dominant inheritance of FEVR. The prevalence and impact of large deletions/duplications of TSPAN12 on FEVR patients is unknown. To glean better insight of TSPAN12 on FEVR pathology, herein, we describe three FEVR patients with TSPAN12 deletions. Methods: Thirty-three Korean FEVR patients, who previously screened negative for TSPAN12 mutations, mutations in other FEVR-associated genes such as NDP, FZD4, LRP5, and large deletions and duplications of NDP, FZD4, and LRP5, were selected for TSPAN12 large deletion and duplication analyses...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27922964/the-effect-of-uniaxial-mechanical-stretch-on-wnt-%C3%AE-catenin-pathway-in-bone-mesenchymal-stem-cells
#17
Chuang Zhao, Yunfeng Li, Xuemei Wang, Shujuan Zou, Jing Hu, En Luo
Wnt/β-catenin signal is required in bone formation and remodling, but little is known about whether Wnt/β-catenin signal could promote osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) after uniaxial mechanical stretch. In this study, rat BMSCs were identified by flow cytometry and used for mechanical stretch. A custom-made uniaxial dynamic stretch apparatus was applied for rat BMSCs stretch. There were 2 groups in the study: the mechanical stretch group and the nonstretch control group...
January 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/27833587/a-candidate-gene-association-study-of-bone-mineral-density-in-an-iranian-population
#18
Seyed Alireza Dastgheib, Alison Gartland, Seyed Mohammad Bagher Tabei, Gholamhossein Ranjbar Omrani, Marion Dawn Teare
The genetic epidemiology of variation in bone mineral density (BMD) and osteoporosis is not well studied in Iranian populations and needs more research. We report a candidate gene association study of BMD variation in a healthy cross-sectional study of 501 males and females sampled from the Iranian Multi-Centre Osteoporosis Study, Shiraz, Iran. We selected to study the association with 21 single nucleotide polymorphisms (SNPs) located in the 7 candidate genes LRP5, RANK, RANKL, OPG, P2RX7, VDR, and ESR1. BMD was measured at the three sites L2-L4, neck of femur, and total hip...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27821587/activation-proliferation-associated-protein-2-caprin-2-positively-regulates-cdk14-cyclin-y-mediated-lipoprotein-receptor-related-protein-5-and-6-lrp5-6-constitutive-phosphorylation
#19
Xin Wang, Yingying Jia, Cong Fei, Xiaomin Song, Lin Li
Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are co-receptors for Wnt ligands. Upon ligand binding, LRP5/6 undergo glycogen synthase kinase 3 (GSK3)/casein kinase I (CKI)-mediated phosphorylation at multiple PPP(S/T)P motifs in the intracellular domain, which is essential for canonical Wnt signal transduction. On the other hand, in the Wnt-off state, the mitosis-specific CDK14-Cyclin Y kinase complex phosphorylates Ser-1490 of LRP5/6 at G2/M, thereby priming the receptor for Wnt-induced phosphorylation...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27803037/opposing-roles-of-wnt-inhibitors-igfbp-4-and-dkk1-in-cardiac-ischemia-by-differential-targeting-of-lrp5-6-and-%C3%AE-catenin
#20
Da Wo, Jinhui Peng, Dan-Ni Ren, Liman Qiu, Jinxiao Chen, Ye Zhu, Yingjing Yan, Hongwei Yan, Jian Wu, En Ma, Tao P Zhong, Yihan Chen, Zhongmin Liu, Shangfeng Liu, Luoquan Ao, Zhenping Liu, Cizhong Jiang, Jun Peng, Yunzeng Zou, Qirong Qian, Weidong Zhu
BACKGROUND: Myocardial infarction is one of the leading causes of morbidity and mortality worldwide, triggering irreversible myocardial cell damage and heart failure. The role of low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) as coreceptors of the Wnt/β-catenin pathway in the adult heart remain unknown. Insulin-like growth factor binding protein 4 and dickkopf-related protein 1 (Dkk1) are 2 secreted LRP5/6 binding proteins that play a crucial role in heart development through preventing Wnt/β-catenin pathway activation...
December 13, 2016: Circulation
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