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https://www.readbyqxmd.com/read/28432956/introduction-of-n-cadherin-binding-motif-to-alginate-hydrogels-for-controlled-stem-cell-differentiation
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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-progenitors-cells
#8
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 new-born (P0) 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
#9
Chunjiang Yu, Melanie Seaton, Scott Letendre, Robert Heaton, Lena Al-Harthi
OBJECTIVE: DKK1 is a soluble antagonist of the Wnt pathway. It binds to and sequesters LRP5/6 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+ individuals. We evaluated here the relationship between plasma DKK1 and global NCI. METHODS: Plasma samples and data from 41 HIV+ and 42 HIV- adults were obtained from the University of California, San Diego...
March 29, 2017: AIDS
https://www.readbyqxmd.com/read/28356706/a-mutagenesis-derived-lrp5-mouse-mutant-with-abnormal-retinal-vasculature-and-low-bone-mineral-density
#10
Jeremy R Charette, Sarah E Earp, Brent A Bell, Cheryl L Ackert-Bicknell, Dana A Godfrey, Sujata Rao, Bela Anand-Apte, Patsy M Nishina, Neal S Peachey
PURPOSE: Familial exudative vitreoretinopathy (FEVR) is caused by mutations in the genes encoding low-density lipoprotein receptor-related protein (LRP5) or its interacting partners, namely frizzled class receptor 4 (FZD4) and norrin cystine knot growth factor (NDP). Mouse models for Lrp5, Fzd4, and Ndp have proven to be important for understanding the retinal pathophysiology underlying FEVR and systemic abnormalities related to defective Wnt signaling. Here, we report a new mouse mutant, tvrm111B, which was identified by electroretinogram (ERG) screening of mice generated in the Jackson Laboratory Translational Vision Research Models (TVRM) mutagenesis program...
2017: Molecular Vision
https://www.readbyqxmd.com/read/28341377/lrp5-from-bedside-to-bench-to-bone
#11
Bart O Williams
A role for Low-density lipoprotein related receptor 5 (LRP5) in human bone was first established by the identification of genetic alterations that led to dramatic changes in human bone mass. Shortly thereafter, mutations that altered the function of the Sclerostin (SOST) gene were also associated with altered human bone mass. Subsequent studies of LRP5 and Sclerostin have provided important insights into the mechanisms by which these proteins regulate skeletal homeostasis. Sclerostin normally binds to LRP5 and the related LRP6 protein and prevents their activation by Wnt ligands...
March 21, 2017: Bone
https://www.readbyqxmd.com/read/28339498/enhancement-of-osteogenic-differentiation-of-rat-adipose-tissue-derived-mesenchymal-stem-cells-by-zinc-sulphate-under-electromagnetic-field-via-the-pka-erk1-2-and-wnt-%C3%AE-catenin-signaling-pathways
#12
Ezzatollah Fathi, Raheleh Farahzadi
Zinc ion as an essential trace element and electromagnetic fields (EMFs) has been reported to be involved in the regulation of bone metabolism. The aim of this study was to elucidate the effects of zinc sulphate (ZnSO4) on the osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ADSCs) in the presence of EMF as a strategy in osteoporosis therapy. Alkaline phophatase (ALP) activity measurement, calcium assay and expression of several osteoblastic marker genes were examined to assess the effect of ZnSO4 on the osteogenic differentiation of ADSCs under EMF...
2017: PloS One
https://www.readbyqxmd.com/read/28332354/cyclized-oligopeptide-targeting-lrp5-6-dkk1-interaction-reduces-the-growth-of-tumor-burden-in-a-multiple-myeloma-mouse-model
#13
Bo Mi Park, Eun Jin Kim, Hee Jin Nam, Dongdong Zhang, Chu Hyun Bae, Myeongmo Kang, Heeyoun Kim, Weontae Lee, Bjarne Bogen, Sung Kil Lim
PURPOSE: Dickkopf 1 (DKK1) has been extensively investigated in mouse models of multiple myeloma, which results in osteolytic bone lesions. Elevated DKK1 levels in bone marrow plasma and serum inhibit the differentiation of osteoblast precursors. Present pharmaceutical approaches to target bone lesions are limited to antiresorptive agents. In this study, we developed a cyclized oligopeptide against DKK1-low density lipoprotein receptor-related protein (LRP) 5/6 interaction and tested the effects of the oligopeptide on tumor burden...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28303247/effect-of-wnt-signaling-on-the-differentiation-of-islet-%C3%AE-cells-from-adipose-derived-stem-cells
#14
Hefei Wang, Yu Ren, Xiao Hu, Min Ma, Xiao Wang, Hao Liang, Dongjun Liu
The Wnt signaling is critical for pancreatic development and islet function; however, its precise effects on the development and function of the β-cells remain controversial. Here we examined mRNA and protein expression of components of the Wnt signaling throughout the differentiation of islet β-cells from adipose-derived stem cells (ADSCs). After induction, ADSCs expressed markers of β-cells, including the insulin, PDX1, and glucagon genes, and the PDX1, CK19, nestin, insulin, and C-peptide proteins, indicating their successful differentiation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28283687/impact-of-gain-of-function-mutations-in-the-low-density-lipoprotein-receptor-related-protein-5-lrp5-on-glucose-and-lipid-homeostasis
#15
D Foer, M Zhu, R L Cardone, C Simpson, R Sullivan, S Nemiroff, G Lee, R G Kibbey, K F Petersen, K L Insogna
LRP5 loss-of-function mutations have been shown to cause profound osteoporosis and have been associated with impaired insulin sensitivity and dysregulated lipid metabolism. We hypothesized that gain-of-function mutations in LRP5 would also affect these parameters. We therefore studied individuals with LRP5 gain-of-function mutations exhibiting high bone mass (HBM) phenotypes and found that while there was no detected change in insulin sensitivity, there was a significant reduction in serum LDL. INTRODUCTION: Wnt signaling through LRP5 represents a newly appreciated metabolic pathway, which potentially represents a target for drug discovery in type 2 diabetes and hyperlipidemia...
March 10, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28273524/altered-bone-microarchitecture-and-gene-expression-profile-due-to-calcium-deficiency-in-a-mouse-model-of-myeloma
#16
Hélène Libouban, Daniel Chappard
It is not clear why patients with an indolent form of multiple myeloma (MM) develop into an aggressive form with poor prognostic. We investigated the effect of a dietary calcium deficiency on tumor growth, osteolysis and gene expression in the 5T2MM murine model. Two groups of C57BL/KaLwRij mice received 5T2MM cells and started a diet with normal (0.8%; "normal-Ca-MM") or low calcium content (0.05%; "low-Ca-MM"). Two control groups (without 5T2MM cells) received either a normal or low calcium diet (normal-Ca and low-Ca groups)...
May 2017: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/28251098/digenic-heterozygous-mutations-in-eys-lrp5-in-a-chinese-family-with-retinitis-pigmentosa
#17
Feng-Juan Gao, Sheng-Hai Zhang, Jun-Yi Chen, Ge-Zhi Xu, Ji-Hong Wu
No abstract text is available yet for this article.
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28242765/a-novel-role-for-the-wnt-inhibitor-apcdd1-in-adipocyte-differentiation-implications-for-diet-induced-obesity
#18
Nicole K H Yiew, Tapan K Chatterjee, Yao Liang Tang, Rod Pellenberg, Brian K Stansfield, Zsolt Bagi, David J Fulton, David W Stepp, Weiqin Chen, Vijay Patel, Vinayak M Kamath, Sheldon E Litwin, David Y Hui, Steven M Rudich, Ha Won Kim, Neal L Weintraub
Impaired adipogenic differentiation during diet-induced obesity (DIO) promotes adipocyte hypertrophy and inflammation, thereby contributing to metabolic disease. Adenomatosis polyposis coli down-regulated 1 (APCDD1) has recently been identified as an inhibitor of Wnt signaling, a key regulator of adipogenic differentiation. Here we report a novel role for APCDD1 in adipogenic differentiation via repression of Wnt signaling and an epigenetic linkage between miR-130 and APCDD1 in DIO. APCDD1 expression was significantly up-regulated in mature adipocytes compared with undifferentiated preadipocytes in both human and mouse subcutaneous adipose tissues...
April 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28240364/n-cadherin-regulation-of-bone-growth-and-homeostasis-is-osteolineage-stage-specific
#19
Francesca Fontana, Cynthia L Hickman-Brecks, Valerie S Salazar, Leila Revollo, Grazia Abou-Ezzi, Susan K Grimston, Sung Yeop Jeong, Marcus Watkins, Manuela Fortunato, Yael Alippe, Daniel C Link, Gabriel Mbalaviele, Roberto Civitelli
N-cadherin inhibits osteogenic cell differentiation and canonical Wnt/β-catenin signaling in vitro. However, in vivo both conditional Cdh2 ablation and overexpression in osteoblasts lead to low bone mass. We tested the hypothesis that N-cadherin has different effects on osteolineage cells depending upon their differentiation stage. Embryonic conditional osteolineage Cdh2 deletion in mice results in defective growth, low bone mass, and reduced osteoprogenitor number. These abnormalities are prevented by delaying Cdh2 ablation until 1 month of age, thus targeting only committed and mature osteoblasts, suggesting they are the consequence of N-cadherin deficiency in osteoprogenitors...
February 27, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28223538/tissue-transglutaminase-induces-epithelial-mesenchymal-transition-and-the-acquisition-of-stem-cell-like-characteristics-in-colorectal-cancer-cells
#20
Oluseyi Ayinde, Zhuo Wang, Martin Griffin
Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT...
March 21, 2017: Oncotarget
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