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https://www.readbyqxmd.com/read/29159713/tmem88-mediates-inflammatory-cytokines-secretion-by-regulating-jnk-p38-and-canonical-wnt-%C3%AE-catenin-signaling-pathway-in-lx-2-cells
#1
Tao Xu, Lin-Xin Pan, Yun-Xuan Ge, Peng Li, Xiao-Ming Meng, Cheng Huang, Jun Li
Recent data have shown that Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane, interacts with the PDZ domain of disheveled-1 (Dvl-1) in Xenopus embryos. Indeed, TMEM88 might inhibit the canonical Wnt/β-catenin signaling pathway by competing with LRP5/6 for interaction with Dvl-1. TMEM88 plays a crucial role in regulating human stem cell differentiation and embryonic development. Until recently, the function of TMEM88 has been a matter of debate. In this study, we explore the role of TMEM88 in cytokine secretion and the role of the MAPK and Wnt/β-catenin signaling pathway in tumor necrosis factor-alpha (TNF-α)-induced TMEM88 expression in LX-2 cells...
November 20, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29154852/the-mitochondrial-uncoupling-protein-2-gene-is-causal-for-the-spontaneous-polycystic-liver-diseases-in-mice
#2
Misa Hirose, Paul Schilf, Sarah Rohde, Yask Gupta, Tiphaine Sancerni, Marie-Clotilde Alves-Guerra, Christian Sina, Robert Jaster, Bruno Miroux, Saleh M Ibrahim
Polycystic liver diseases (PCLDs) are autosomal dominant disorders. To date, 3 genes are known to be associated with the disease, SEC63 and PRKCSH and LRP5. Here, we report that mice deficient in the mitochondrial uncoupling protein 2 gene (Ucp2(-/-)) spontaneously developed PCLDs when they were over 12months old. Macroscopical observation, blood chemistry as well as histopathological analysis demonstrated the PCLDs found in Ucp2(-/-) mice were very similar to the findings in human PCLDs. This is the first report describing the gene encoding mitochondrial protein is causative for PCLDs...
November 14, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29154126/the-wnt-inhibitor-apcdd1-coordinates-vascular-remodeling-and-barrier-maturation-of-retinal-blood-vessels
#3
Jenna Mazzoni, Julian R Smith, Sanjid Shahriar, Tyler Cutforth, Bernardo Ceja, Dritan Agalliu
Coordinating angiogenesis with acquisition of tissue-specific properties in endothelial cells is essential for vascular function. In the retina, endothelial cells form a blood-retina barrier by virtue of tight junctions and low transcytosis. While the canonical Norrin/Fz4/Lrp5/6 pathway is essential for angiogenesis, vascular remodeling, and barrier maturation, how these diverse processes are coordinated remains poorly understood. Here we demonstrate that Apcdd1, a negative regulator of Wnt/β-catenin signaling, is expressed in retinal endothelial cells during angiogenesis and barrier formation...
November 4, 2017: Neuron
https://www.readbyqxmd.com/read/29131652/novel-homozygous-lrp5-mutations-in-mexican-patients-with-osteoporosis-pseudoglioma-syndrome
#4
Mirena C Astiazarán, María Cervantes-Sodi, Erick Rebolledo-Enríquez, Oscar Chacón-Camacho, Vanessa Villegas, Juan Carlos Zenteno
AIMS: Osteoporosis-pseudoglioma syndrome (OPPG) is an uncommon autosomal recessive disorder characterized by the rare association of early-onset osteoporosis and severe ocular abnormalities such as persistent fetal vasculature and microphthalmia. Biallelic mutations in the low-density lipoprotein receptor-related protein-5 gene (LRP5) have been associated with OPPG. We present clinical and genetic data of three Mexican OPPG patients, a pair of sibs, and a sporadic case. MATERIALS AND METHODS: Three patients underwent clinical examination, including a complete ophthalmic evaluation...
November 13, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29123202/potential-damaging-mutation-in-lrp5-from-genome-sequencing-of-the-first-reported-chimpanzee-with-the-chiari-malformation
#5
Manuel Solis-Moruno, Marc de Manuel, Jessica Hernandez-Rodriguez, Claudia Fontsere, Alba Gomara-Castaño, Cristina Valsera-Naranjo, Dietmar Crailsheim, Arcadi Navarro, Miquel Llorente, Laura Riera, Olga Feliu-Olleta, Tomas Marques-Bonet
The genus Pan is the closest related to humans (Homo sapiens) and it includes two species: Pan troglodytes (chimpanzees) and Pan paniscus (bonobos). Different characteristics, some of biomedical aspect, separate them from us. For instance, some common human medical conditions are rare in chimpanzees (menopause, Alzheimer disease) although it is unclear to which extent longevity plays an active role in these differences. However, both humans and chimpanzees present similar pathologies, thus, understanding traits in chimpanzees can help unravel the molecular basis of human conditions...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29123193/characterization-of-mammary-specific-disruptions-for-tph1-and-lrp5-during-murine-lactation
#6
Samantha R Weaver, Nicholas J Jury, Karen A Gregerson, Nelson D Horseman, Laura L Hernandez
Serotonin is a homeostatic regulator of the mammary gland during lactation. The contribution of mammary-derived serotonin to circulating serum serotonin concentrations was previously unknown. We have developed mice with mammary-specific disruptions of tryptophan hydroxylase 1 (Tph1) or low-density lipoprotein receptor-related protein 5 (Lrp5) that are induced during late pregnancy and lactation via use of the whey acidic protein (WAP)-Cre cre-lox system. Our objective was to characterize dams with a lactation- and mammary-specific disruption of Lrp5 (WAP-Cre × Lrp5 (FL/FL)) or Tph1 (WAP-Cre × Tph1 (FL/FL))...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107218/dual-targeting-wnt-and-upa-receptors-using-peptide-conjugated-ultra-small-nanoparticle-drug-carriers-inhibited-cancer-stem-cell-phenotype-in-chemo-resistant-breast-cancer
#7
Jasmine Miller-Kleinhenz, Xiangxue Guo, Weiping Qian, Hongyu Zhou, Erica N Bozeman, Lei Zhu, Xin Ji, Y Andrew Wang, Toncred Styblo, Ruth O'Regan, Hui Mao, Lily Yang
Heterogeneous tumor cells, high incidence of tumor recurrence, and decrease in overall survival are the major challenges for the treatment of chemo-resistant breast cancer. Results of our study showed differential chemotherapeutic responses among breast cancer patient derived xenograft (PDX) tumors established from the same patients. All doxorubicin(Dox)-resistant tumors expressed higher level of cancer stem-like cell biomarkers, including CD44, Wnt and its receptor LRP5/6, relative to Dox-sensitive tumors...
October 21, 2017: Biomaterials
https://www.readbyqxmd.com/read/29102319/wnt-signaling-pathway-correlates-with-ossification-of-the-spinal-ligament-a-microrna-array-and-immunohistochemical-study
#8
Takafumi Yayama, Kanji Mori, Noriaki Okumura, Kazuya Nishizawa, Kosuke Kumagai, Akira Nakamura, Shinji Imai
BACKGROUND: Ossification of the posterior longitudinal ligament or the ligamentum flavum parallels endochondral ossification. Cell differentiation at the ossification front is known to be important during this process, although the factors regulating its initiation and progression are still unclear. The purpose of this study was to identify factors important for the regulation of chondrocyte/osteoblast differentiation during spinal ossification. METHODS: Ligamentum flavum tissue was isolated from 25 patients who underwent decompressive surgery for cervical ossification of the posterior longitudinal ligament...
October 25, 2017: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
https://www.readbyqxmd.com/read/29077850/%C3%AE-catenin-directs-long-chain-fatty-acid-catabolism-in-the-osteoblasts-of-male-mice
#9
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
https://www.readbyqxmd.com/read/29038835/interaction-between-lrp5-and-periostin-gene-polymorphisms-on-serum-periostin-levels-and-cortical-bone-microstructure
#10
J Pepe, N Bonnet, F R Herrmann, E Biver, R Rizzoli, T Chevalley, S L Ferrari
We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. PURPOSE: The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women...
October 16, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/29038287/genetic-complexity-of-autosomal-dominant-polycystic-kidney-and-liver-diseases
#11
Emilie Cornec-Le Gall, Vicente E Torres, Peter C Harris
Data indicate significant phenotypic and genotypic overlap, plus a common pathogenesis, between two groups of inherited disorders, autosomal dominant polycystic kidney diseases (ADPKD), a significant cause of ESRD, and autosomal dominant polycystic liver diseases (ADPLD), which result in significant PLD with minimal PKD. Eight genes have been associated with ADPKD (PKD1 and PKD2), ADPLD (PRKCSH, SEC63, LRP5, ALG8, and SEC61B), or both (GANAB). Although genetics is only infrequently used for diagnosing these diseases and prognosing the associated outcomes, its value is beginning to be appreciated, and the genomics revolution promises more reliable and less expensive molecular diagnostic tools for these diseases...
October 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28980049/effects-of-endogenous-hypercortisolism-on-bone-mrna-and-microrna-expression-in-humans
#12
Z E Belaya, T A Grebennikova, G A Melnichenko, A G Nikitin, A G Solodovnikov, O I Brovkina, A U Grigoriev, L Y Rozhinskaya, I I Dedov
Hypercortisolism in humans suppresses osteoblastogenesis and osteoblast function through the upregulation of Wnt-signaling antagonists (sclerostin, Dkk1) and changes in microRNAs levels (miR-125b-5p, miR-218-5p, miR-34a-5p, miR-188-3p, miR-199a-5p) which are associated with mesenchymal stem-cell commitment to adipocytes or cartilage cells over the osteoblasts. INTRODUCTION: The purpose of this study was to evaluate the responses of bone to chronic glucocorticoid (GC) excess by measuring the levels of selected mRNA and microRNA (miR) in bone samples of patients with Cushing's disease (CD)...
October 4, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28974197/analysis-of-snp-snp-interactions-and-bone-quantitative-ultrasound-parameter-in-early-adulthood
#13
María Correa-Rodríguez, Sebastien Viatte, Jonathan Massey, Jacqueline Schmidt-RioValle, Blanca Rueda-Medina, Gisela Orozco
BACKGROUND: Osteoporosis individual susceptibility is determined by the interaction of multiple genetic variants and environmental factors. The aim of this study was to conduct SNP-SNP interaction analyses in candidate genes influencing heel quantitative ultrasound (QUS) parameter in early adulthood to identify novel insights into the mechanism of disease. METHODS: The study population included 575 healthy subjects (mean age 20.41; SD 2.36). To assess bone mass QUS was performed to determine Broadband ultrasound attenuation (BUA, dB/MHz)...
October 3, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/28973524/liver-cyst-gene-knockout-in-cholangiocytes-inhibits-cilium-formation-and-wnt-signaling
#14
Edgar S Wills, René H M Te Morsche, Jeroen van Reeuwijk, Nicola Horn, Iris Geomini, Liyanne F M van de Laarschot, Dorus A Mans, Marius Ueffing, Karsten Boldt, Joost P H Drenth, Ronald Roepman
Mutations in the PRKCSH, SEC63 and LRP5 genes cause autosomal dominant polycystic liver disease (ADPLD). The proteins products of PRKCSH (alias GIIB) and SEC63 function in protein quality control and processing in the endoplasmic reticulum (ER), while LRP5 is implicated in Wnt/β-catenin signaling. To identify common denominators in the PLD pathogenesis, we mapped the PLD interactome by affinity proteomics, employing both HEK293T cells and H69 cholangiocytes. Identification of known complex members, such as glucosidase IIA (GIIA) for PRKCSH, and SEC61A1 and SEC61B for SEC63, confirmed the specificity of the analysis...
November 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28971234/a-novel-dominant-col11a1-mutation-in-a-child-with-stickler-syndrome-type-ii-is-associated-with-recurrent-fractures
#15
M G Vogiatzi, D Li, L Tian, J P Garifallou, C E Kim, H Hakonarson, M A Levine
This case describes a child with blindness, recurrent low-impact fractures, low bone mass, and intermittent joint pain who was found to have a novel missense mutation in COL11A1, consistent with Stickler syndrome type II. The case illustrates the phenotypic variability of the syndrome, which may include increased fragility in childhood. INTRODUCTION: Stickler syndrome type II is an autosomal dominant disorder caused by mutations in the gene that encodes the type XI collagen chain α1 (COL11A1)...
October 3, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28941231/assembly-and-architecture-of-the-wnt-%C3%AE-catenin-signalosome-at-the-membrane
#16
REVIEW
Zachary J DeBruine, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is initiated by a ternary Wnt-Frizzled-LRP5/6 binding event. The resulting conformational changes in the Frizzled (FZD) and LRP5/6 receptors promote assembly of an intracellular signalosome driven by Dishevelled and Axin co-polymerization. Recent evidence suggests that FZD and LRP5/6 participate in assembly of this signalosome by forming regulatory scaffolds for stabilizing Dishevelled and Axin adapters. In this review, we focus on the contributions of Wnts and their receptors in assembly of the signalosome...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28938444/lack-of-lrp5-signaling-in-osteoblasts-sensitizes-male-mice-to-diet-induced-disturbances-in-glucose-metabolism
#17
Soohyun P Kim, Julie L Frey, Zhu Li, Brian C Goh, Ryan C Riddle
Wnt signaling through the low-density lipoprotein-related receptor 5 (Lrp5) coreceptor regulates osteoblast maturation, matrix mineralization, and intermediary metabolism. In the mature osteoblast, signals downstream of Lrp5 are required for normal long-chain fatty acid β-oxidation. Mice rendered deficient for this coreceptor in osteoblasts and osteocytes accumulate body fat with elevated serum lipid levels but retain normal insulin sensitivity. In the present study, we challenged Lrp5-mutant mice with a high-fat diet (HFD) to determine whether they were more susceptible to diet-induced disturbances in glucose homeostasis...
November 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28893644/high-bone-mass-due-to-novel-lrp5-and-amer1-mutations
#18
Alice Costantini, Päivi Kekäläinen, Riikka E Mäkitie, Outi Mäkitie
WNT signaling is a key regulator of bone metabolism and its increased or decreased activity leads to skeletal disorders. Here we describe two patients with high bone mass (HBM) caused by novel mutations in two different WNT pathway components. The first patient is a 53-year-old male with HBM. He was diagnosed at adult age based on significantly increased bone mineral density (BMD). He has undergone several surgeries due to excessive bone in ear canals, bilateral jaw exostoses and mandibular tori. Radiographs show severe cortical thickening of cranial and long bones...
September 8, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/28891484/variable-expressivity-and-response-to-bisphosphonate-therapy-in-a-family-with-osteoporosis-pseudoglioma-syndrome
#19
Karthik B Tallapaka, Prajnya Ranganath, Ashwin Dalal
BACKGROUND: Osteoporosis pseudoglioma syndrome (OPPGS) is a rare autosomal recessive genetic disorder characterised by congenital blindness and osteoporosis, caused by biallelic mutations in the LRP5 gene. CASE CHARACTERISTICS: A consanguineous family with four OPPGS-affected members with variable expressivity. OBSERVATION: A novel homozygous missense pathogenic variant (c.3709C>T) was identified in the LRP5 gene. Good response to biphosphonate therapy was observed in all affected members...
August 15, 2017: Indian Pediatrics
https://www.readbyqxmd.com/read/28879758/light-controlled-bmsc-sheet-implant-complexes-with-improved-osteogenesis-via-an-lrp5-%C3%AE-catenin-runx2-regulatory-loop
#20
Zhiwei Jiang, Huiming Wang, Ke Yu, Yuting Feng, Ying Wang, Tingben Huang, Kaichen Lai, Yue Xi, Guoli Yang
The combination of bone marrow mesenchymal stem cell (BMSC) sheets and titanium implants (BMSC sheet-implant complexes) can accelerate osseointegration. However, methods of fabricating BMSC sheet-implant complexes are quite limited, and the survival of BMSC sheet-implant complexes is one of the key barriers. Here, we show that a light-controlled fabricating system can generate less injured BMSC sheet-implant complexes with improved viability and osteogenesis and that noninvasive monitoring of the viability of BMSC sheet-implant complexes using a lentiviral delivery system is feasible...
October 11, 2017: ACS Applied Materials & Interfaces
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