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https://www.readbyqxmd.com/read/28629266/polygonatum-sibiricum-polysaccharide-promotes-osteoblastic-differentiation-through-the-erk-gsk-3%C3%AE-%C3%AE-catenin-signaling-pathway-in-vitro
#1
Xiaoming Peng, Jichen He, Jinmin Zhao, Yunle Wu, Xiongzhi Shi, Li Du, Mengni Nong, Shaohui Zong, Gao-Feng Zeng
Natural compound Polygonatum sibiricum polysaccharide (PSP) has a variety of biological actions such as reducing blood fat, antitumor, antioxidant activities, and enhancing immune function. In our previous study has revealed that PSP can promote osteoblastic differentiation in bone mesenchymal stem cells (BMSCs) by increasing nuclear accumulation of β-catenin. This study was designed to investigate that PSP can upregulate nuclear β-catenin, which was prevented by inhibiting glycogen synthase kinase 3β (GSK-3β) activity, by effectively activating Wnt signaling independent of low-density lipoprotein receptor-related protein (LRP5) ...
June 19, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28607813/differential-involvement-of-wnt-signaling-in-bmp-regulation-of-cancellous-versus-periosteal-bone-growth
#2
Guangxu He, Yu Shi, Joohyun Lim, Teresita Bellido, Jiangdong Ni, Fanxin Long
Bone morphogenetic proteins (Bmp) are well-known to induce bone formation following chondrogenesis, but the direct role of Bmp signaling in the osteoblast lineage is not completely understood. We have recently shown that deletion of the receptor Bmpr1a in the osteoblast lineage with Dmp1-Cre reduces osteoblast activity in general but stimulates proliferation of preosteoblasts specifically in the cancellous bone region, resulting in diminished periosteal bone growth juxtaposed with excessive cancellous bone formation...
2017: Bone Research
https://www.readbyqxmd.com/read/28575650/defects-in-the-cell-signaling-mediator-%C3%AE-catenin-cause-the-retinal-vascular-condition-fevr
#3
Evangelia S Panagiotou, Carla Sanjurjo Soriano, James A Poulter, Emma C Lord, Denisa Dzulova, Hiroyuki Kondo, Atsushi Hiyoshi, Brian Hon-Yin Chung, Yoyo Wing-Yiu Chu, Connie H Y Lai, Mark E Tafoya, Dyah Karjosukarso, Rob W J Collin, Joanne Topping, Louise M Downey, Manir Ali, Chris F Inglehearn, Carmel Toomes
Familial exudative vitreoretinopathy (FEVR) is an inherited blinding disorder characterized by the abnormal development of the retinal vasculature. The majority of mutations identified in FEVR are found within four genes that encode the receptor complex (FZD4, LRP5, and TSPAN12) and ligand (NDP) of a molecular pathway that controls angiogenesis, the Norrin-β-catenin signaling pathway. However, half of all FEVR-affected case subjects do not harbor mutations in these genes, indicating that further mutated genes remain to be identified...
June 1, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28546512/wnt5a-promotes-frizzled-4-signalosome-assembly-by-stabilizing-cysteine-rich-domain-dimerization
#4
Zachary J DeBruine, Jiyuan Ke, Kaleeckal G Harikumar, Xin Gu, Peter Borowsky, Bart O Williams, Wenqing Xu, Laurence J Miller, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal "thumb" and a disulfide-stabilized C-terminal "index finger," yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD4) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers...
May 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28513615/exome-sequencing-of-two-italian-pedigrees-with-non-isolated-chiari-malformation-type-i-reveals-candidate-genes-for-cranio-facial-development
#5
Elisa Merello, Lorenzo Tattini, Alberto Magi, Andrea Accogli, Gianluca Piatelli, Marco Pavanello, Domenico Tortora, Armando Cama, Zoha Kibar, Valeria Capra, Patrizia De Marco
Chiari malformation type I (CMI) is a congenital abnormality of the cranio-cerebral junction with an estimated incidence of 1 in 1280. CMI is characterized by underdevelopment of the occipital bone and posterior fossa (PF) and consequent cerebellar tonsil herniation. The presence for a genetic basis to CMI is supported by many lines of evidence. The cellular and molecular mechanisms leading to CM1 are poorly understood. The occipital bone formation is dependent on complex interactions between genes and molecules with pathologies resulting from disruption of this delicate process...
May 17, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28501564/wntless-promotes-bladder-cancer-growth-and-acts-synergistically-as-a-molecular-target-in-combination-with-cisplatin
#6
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/28494495/mutations-in-lrp5-fzd4-tspan12-ndp-znf408-or-kif11-genes-account-for-38-7-of-chinese-patients-with-familial-exudative-vitreoretinopathy
#7
Feng-Qin Rao, Xue-Bi Cai, Fei-Fei Cheng, Wan Cheng, Xiao-Long Fang, Na Li, Xiu-Feng Huang, Li-Hong Li, Zi-Bing Jin
Purpose: Familial exudative vitreoretinopathy (FEVR) is a severe hereditary retinal disorder characterized by defects in retinal vascular development. To date, six genes have been reported to be responsible for this disease, including LRP5, FZD4, TSPAN12, NDP, ZNF408, and KIF11. The purpose of our study was to investigate the genetic defects in Chinese patients with FEVR through mutational analyses of 31 pedigrees. Methods: Clinical data and peripheral blood were collected from 31 pedigrees with FEVR...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28487939/identification-of-novel-genes-associated-with-fracture-healing-in-osteoporosis-induced-by-krm2-overexpression-or-lrp5-deficiency
#8
Feng Gao, Feng Xu, Dankai Wu, Jieping Cheng, Peng Xia
The aim of the present study was to screen potential key genes associated with osteoporotic fracture healing. The microarray data from the Gene Expression Omnibus database accession number GSE51686, were downloaded and used to identify differentially expressed genes (DEGs) in fracture callus tissue samples obtained from the femora of type I collagen (Col1a1)‑kringle containing transmembrane protein 2 (Krm2) mice and low density lipoprotein receptor‑related protein 5‑/‑ (Lrp5‑/‑) transgenic mice of osteoporosis compared with those in wild‑type (WT) mice...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28479140/cannabidiol-administration-reduces-sublesional-cancellous-bone-loss-in-rats-with-severe-spinal-cord-injury
#9
Dehao Li, Zilin Lin, Qingyi Meng, Kun Wang, Jiajia Wu, Hongda Yan
Patients with spinal cord injury (SCI) undergo severe loss of bone mineral below the level of lesion, and data on available treatment options after SCI is scarce. The aim of this work was to investigate the therapeutic effect of cannabidiol (CBD), a non-psychoactive cannabis, on sublesional bone loss in a rat model of SCI. The adult male rats were exposed to surgical transection of the cord and treated with CBD for consecutive 14 days. It was found that CBD treatment elevated the serum levels of osteocalcin, reduced the serum levels of collagen type I cross-linked C-telopeptide, and enhanced bone mineral density of tibiae and femurs...
May 4, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28467820/non-equivalence-of-wnt-and-r-spondin-ligands-during-lgr5-intestinal-stem-cell-self-renewal
#10
Kelley S Yan, Claudia Y Janda, Junlei Chang, Grace X Y Zheng, Kathryn A Larkin, Vincent C Luca, Luis A Chia, Amanda T Mah, Arnold Han, Jessica M Terry, Akifumi Ootani, Kelly Roelf, Mark Lee, Jenny Yuan, Xiao Li, Christopher R Bolen, Julie Wilhelmy, Paige S Davies, Hiroo Ueno, Richard J von Furstenberg, Phillip Belgrader, Solongo B Ziraldo, Heather Ordonez, Susan J Henning, Melissa H Wong, Michael P Snyder, Irving L Weissman, Aaron J Hsueh, Tarjei S Mikkelsen, K Christopher Garcia, Calvin J Kuo
The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28467818/surrogate-wnt-agonists-that-phenocopy-canonical-wnt-and-%C3%AE-catenin-signalling
#11
Claudia Y Janda, Luke T Dang, Changjiang You, Junlei Chang, Wim de Lau, Zhendong A Zhong, Kelley S Yan, Owen Marecic, Dirk Siepe, Xingnan Li, James D Moody, Bart O Williams, Hans Clevers, Jacob Piehler, David Baker, Calvin J Kuo, K Christopher Garcia
Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28432956/introduction-of-n-cadherin-binding-motif-to-alginate-hydrogels-for-controlled-stem-cell-differentiation
#12
Jae Won Lee, Hyoseok An, Kuen Yong Lee
Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif...
April 9, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28432596/exploiting-the-wnt-signaling-pathway-for-clinical-purposes
#13
REVIEW
Mark L Johnson, Robert R Recker
PURPOSE OF REVIEW: The goal of this paper is to evaluate critically the literature published over the past 3 years regarding the Wnt signaling pathway. The Wnt pathway was found to be involved in bone biology in 2001-2002 with the discovery of a (G171V) mutation in the lipoprotein receptor-related protein 5 (LRP5) that resulted in high bone mass and another mutation that completely inactivated Lrp5 function and resulted in osteoporosis pseudoglioma syndrome (OPPG). The molecular biology has been complex, and very interesting...
April 21, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28425175/haemorrhagic-snake-venom-metalloproteases-and-human-adams-cleave-lrp5-6-which-disrupts-cell-cell-adhesions-in-vitro-and-induces-haemorrhage-in-vivo
#14
Tadahiko Seo, Taketo Sakon, Shiori Nakazawa, Asuka Nishioka, Kohei Watanabe, Kaori Matsumoto, Mari Akasaka, Narumi Shioi, Hitoshi Sawada, Satohiko Araki
Snake venom metalloproteases (SVMPs) are members of the a disintegrin and metalloprotease (ADAM) family of proteins, as they possess similar domains. SVMPs are known to elicit snake venom-induced haemorrhage; however, the target proteins and cleavage sites are not known. In this work, we identified a target protein of vascular apoptosis-inducing protein 1 (VAP1), an SVMP, relevant to its ability to induce haemorrhage. VAP1 disrupted cell-cell adhesions by relocating VE-cadherin and γ-catenin from the cell-cell junction to the cytosol, without inducing proteolysis of VE-cadherin...
April 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28420620/identification-of-lrp5-mutations-in-families-with-familial-exudative-vitreoretinopathy
#15
Liu Yuqing, Zhu Xiong, Li Shujin, Yang Yeming, Yang Mu, Zhao Peiquan, Zhu Xianjun
Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease characterized by defects in the development of periphery retinal vessels. However, the clinical phenotypes of FEVR vary widely from asymptomatic to complete blindness. We analyzed patients from three Chinese families and one sporadic patient with FEVR to investigate the clinical features and disease-causing mutations. Ocular phenotypes included increased ramification of the peripheral retinal vessels, a peripheral avascular zone, inferotemporal dragging of the optic disc and macula, and retinal folds...
March 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28418602/expression-of-low-density-lipoprotein-related-receptors-5-and-6-lrp5-6-in-psoriasis-skin
#16
Albert Duvetorp, Renate Slind Olsen, Helena Nyström, Marita Skarstedt, Olaf Dienus, Ulrich Mrowietz, Jan Söderman, Oliver Seifert
Low-density lipoprotein-related receptors 5 and 6 (LRP5/6) are transmembrane receptors with key functions in canonical Wnt signaling. Wnt ligands are thought to play an important role in innate immunity and psoriasis and recent studies assigned LRP5/6 anti-inflammatory properties. The objective of this study was to investigate the expression of LRP5 and LRP6 in lesional and non-lesional skin in peripheral blood and in mononuclear cells of patients with chronic plaque type psoriasis compared with control individuals...
April 18, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28378289/molecular-diagnosis-in-children-with-fractures-but-no-extraskeletal-signs-of-osteogenesis-imperfecta
#17
G Bardai, L M Ward, P Trejo, P Moffatt, F H Glorieux, F Rauch
In 26 of 94 individuals (28%) below 21 years of age who had a significant fracture history but did not have extraskeletal features of osteogenesis imperfecta (OI), we detected disease-causing mutations in OI-associated genes. INTRODUCTION: In children who have mild bone fragility but do not have extraskeletal features of OI, it can be difficult to establish a diagnosis on clinical grounds. Here, we assessed the diagnostic yield of genetic testing in this context, by sequencing a panel of genes that are associated with OI...
April 4, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28369098/functional-relevance-for-associations-between-osteoporosis-and-genetic-variants
#18
Kun Liu, Li-Jun Tan, Peng Wang, Xiang-Ding Chen, Li-Hua Zhu, Qin Zeng, Yuan Hu, Hong-Wen Deng
Osteoporosis is characterized by increased bone loss and deterioration of bone microarchitecture, which will lead to reduced bone strength and increased risk of fragility fractures. Previous studies have identified many genetic loci associated with osteoporosis, but functional mechanisms underlying the associations have rarely been explored. In order to explore the potential molecular functional mechanisms underlying the associations for osteoporosis, we performed integrative analyses by using the publically available datasets and resources...
2017: PloS One
https://www.readbyqxmd.com/read/28359679/activation-of-wnt-signaling-increases-numbers-of-enteric-neurons-derived-from-neonatal-mouse-and-human-progenitor%C3%A2-cells
#19
Ying Zhang, Karin Seid, Florian Obermayr, Lothar Just, Peter H Neckel
BACKGROUND & AIMS: Neural stem and progenitor cells from the enteric nervous system (ENS) might serve as a source of cells for treatment of neurogastrointestinal disorders. Before we can use these cells, we must increase our understanding of the signaling mechanisms that regulate proliferation and differentiation. We systematically evaluated the effects of canonical Wnt signaling on proliferation and differentiation of cultured ENS progenitor cells from neonatal mice and humans. METHODS: We isolated ENS progenitors from tunica muscularis of the small intestine of newborn (postnatal day 0) wild-type C57BL/6 mice as well as from Wnt1-Cre2 reporter mice...
March 27, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28358733/plasma-dickkopf-related-protein-1-an-antagonist-of-the-wnt-pathway-is-associated-with-hiv-associated-neurocognitive-impairment
#20
Chunjiang Yu, Melanie Seaton, Scott Letendre, Robert Heaton, Lena Al-Harthi
OBJECTIVE: Dickkopf-related protein 1 (DKK1) is a soluble antagonist of the Wningless (Wnt) pathway. It binds to and sequesters low-density lipoprotein receptor-related proteins 5/6 away from Wnts. Because the Wnt pathway regulates synaptic transmission and plasticity, we hypothesized that increased DKK1 would increase the risk for neurocognitive impairment (NCI) in HIV-positive (HIV) individuals. We evaluated, here, the relationship between plasma DKK1 and global NCI. METHODS: Plasma samples and data from 41 HIV to 42 HIV adults were obtained from the University of California, San Diego, California, USA...
June 19, 2017: AIDS
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