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https://www.readbyqxmd.com/read/29777010/developmental-vascular-regression-is-regulated-by-a-wnt-%C3%AE-catenin-myc-p21-cdkn1a-pathway-that-controls-cell-proliferation-and-cell-death
#1
Gowri Nayak, Yoshinobu Odaka, Vikram Prasad, Alyssa F Solano, Eun-Jin Yeo, Shruti Vemaraju, Jeffery D Molkentin, Andreas Trumpp, Bart Williams, Sujata Rao, Richard A Lang
Normal development requires tight regulation of cell proliferation and cell death. Here, we investigated these control mechanisms in the hyaloid vessels, a temporary vascular network in the mammalian eye that requires a Wnt/β-catenin response for scheduled regression. We investigated whether the hyaloid Wnt response was linked to the oncogene Myc , and the cyclin-dependent kinase inhibitor P21 (CDKN1A), both established regulators of cell cycle progression and cell death. Our analysis showed that the Wnt pathway coreceptors LRP5 and LRP6 have overlapping activities mediating the Wnt/β-catenin signaling in hyaloid vascular endothelial cells (VECs)...
May 18, 2018: Development
https://www.readbyqxmd.com/read/29728620/author-correction-potential-damaging-mutation-in-lrp5-from-genome-sequencing-of-the-first-reported-chimpanzee-with-the-chiari-malformation
#2
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
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29718273/fgf23-regulates-wnt-%C3%AE-catenin-signaling-mediated-osteoarthritis-in-mice-overexpressing-high-molecular-weight-fgf2
#3
Patience Meo Burt, Liping Xiao, Marja M Hurley
Although humans with X-linked hypophosphatemia (XLH) and the Hyp mouse, a murine homologue of XLH, are known to develop degenerative joint disease, the exact mechanism which drives the osteoarthritic (OA) phenotype remains unclear. Mice that overexpress high molecular weight FGF2 isoforms (HMWTg mice) phenocopy both XLH and Hyp including OA with increased fibroblast growth factor 23 (FGF23) production in bone and serum. Since HMWTg cartilage also has increased FGF23 and there is crosstalk between FGF23-Wnt/β-catenin signaling, the purpose of this study was to determine if OA observed in HMWTg mice is due to FGF23 mediated-canonical Wnt signaling in chondrocytes given that both pathways are implicated in OA pathogenesis...
April 26, 2018: Endocrinology
https://www.readbyqxmd.com/read/29709743/a-case-report-of-worth-syndrome-and-chiari-i-malformation-unusual-association-and-surgical-treatment
#4
Martin Andres Merenzon, Matias Agustin Dorman, Pablo Zuliani Sampaolesi, Pablo Alejandro Seoane, Fernando Latorre, Eduardo Roberto Seoane
BACKGROUND: Worth syndrome or Autosomal Dominant Endosteal Hyperostosis (ADEH) is an extremely rare genetic disease involving increased bone density. To the author's knowledge, this is the second case report of a family with neurological involvement associated with this condition along with its surgical treatment. The most effective treatment for clinically significant neurological symptoms in this scenario is currently unknown and there is very sparse experience on surgical treatment for this condition reported in the literature...
April 27, 2018: World Neurosurgery
https://www.readbyqxmd.com/read/29662200/targeting-sphingosine-1-phosphate-lyase-as-an-anabolic-therapy-for-bone-loss
#5
Sarah Weske, Mithila Vaidya, Alina Reese, Karin von Wnuck Lipinski, Petra Keul, Julia K Bayer, Jens W Fischer, Ulrich Flögel, Jens Nelsen, Matthias Epple, Marta Scatena, Edzard Schwedhelm, Marcus Dörr, Henry Völzke, Eileen Moritz, Anke Hannemann, Bernhard H Rauch, Markus H Gräler, Gerd Heusch, Bodo Levkau
Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways...
April 16, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29652990/-analysis-of-pathological-mutation-in-a-chinese-pedigree-affected-with-familial-exudative-vitreoretinopathy
#6
Ning Su, Litao Qin, Hongdan Wang, Hai Xiao, Qiannan Guo, Tao Li, Shixiu Liao
OBJECTIVE: To detect potential mutation in a Chinese pedigree affected with familial exudative vitreoretinopathy (FEVR). METHODS: Clinical data of the pedigree was collected. Coding regions of candidate genes were amplified by PCR and subjected to next generation sequencing (NGS). Suspected mutations were verified by Sanger sequencing and segregation analysis. RESULTS: Two novel heterozygous mutations (c.1695dupC and c.552-563del) were respectively detected in the LRP5 and ZNF408 genes in the proband...
April 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29625972/long-term-electroacupuncture-stimulation-prevents-osteoporosis-in-ovariectomised-osteopaenic-rats-through-multiple-signalling-pathways
#7
Xuefeng Zheng, Yan Nie, Chengtao Sun, Guangwen Wu, Qiaoyan Cai, Shu Huang, Yanping Lin
BACKGROUND: The pathogenic mechanisms of postmenopausal osteoporosis (PMOP) development are complex and are related to multiple cellular signalling transduction pathways. The aim of this study was to compare the effects of electroacupuncture (EA) at GV4/GV6 versus BL20/BL23 on the bones in ovariectomised (OVX) rats to explore the pathways that mediate the effects of EA on bone. METHODS: Forty female Sprague-Dawley rats were allocated to one of four groups (n=10 rats each) that received sham surgery (Sham group), OVX surgery only (OVX group), OVX surgery plus EA at GV4/GV6 (GV group) and OVX surgery plus EA at BL20/BL23 (BL group)...
April 6, 2018: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
https://www.readbyqxmd.com/read/29615567/the-roles-of-the-wnt-antagonists-axin-and-lrp4-during-embryogenesis-of-the-red-flour-beetle-tribolium-castaneum
#8
Romy Prühs, Anke Beermann, Reinhard Schröder
In both vertebrates and invertebrates, the Wnt-signaling pathway is essential for numerous processes in embryogenesis and during adult life. Wnt activity is fine-tuned at various levels by the interplay of a number of Wnt-agonists (Wnt ligands, Frizzled-receptors, Lrp5/6 coreceptors) and Wnt-antagonists (among them Axin, Secreted frizzled and Lrp4) to define anterior-posterior polarity of the early embryo and specify cell fate in organogenesis. So far, the functional analysis of Wnt-pathway components in insects has concentrated on the roles of Wnt-agonists and on the Wnt-antagonist Axin...
October 15, 2017: Journal of Developmental Biology
https://www.readbyqxmd.com/read/29602775/canonical-wnt-signaling-in-cd11c-apcs-regulates-microbiota-induced-inflammation-and-immune-cell-homeostasis-in-the-colon
#9
Daniel Swafford, Arulkumaran Shanmugam, Punithavathi Ranganathan, Mohamed S Hussein, Pandelakis A Koni, Puttur D Prasad, Muthusamy Thangaraju, Santhakumar Manicassamy
Aberrant Wnt/β-catenin signaling occurs in several inflammatory diseases, including inflammatory bowel disease and inflammatory bowel disease-associated colon carcinogenesis. However, its role in shaping mucosal immune responses to commensals in the gut remains unknown. In this study, we investigated the importance of canonical Wnt signaling in CD11c+ APCs in controlling intestinal inflammation. Using a mouse model of ulcerative colitis, we demonstrated that canonical Wnt signaling in intestinal CD11c+ APCs controls intestinal inflammation by imparting an anti-inflammatory phenotype...
March 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29594386/mutational-analysis-uncovers-monogenic-bone-disorders-in-women-with-pregnancy-associated-osteoporosis-three-novel-mutations-in-lrp5-col1a1-and-col1a2
#10
S Butscheidt, A Delsmann, T Rolvien, F Barvencik, M Al-Bughaili, S Mundlos, T Schinke, M Amling, U Kornak, R Oheim
Pregnancy was found to be a skeletal risk factor promoting the initial onset of previously unrecognized monogenic bone disorders, thus explaining a proportion of cases with pregnancy-associated osteoporosis. Therapeutic measures should focus in particular on the normalization of the disturbed calcium homeostasis in order to enable the partial skeletal recovery. INTRODUCTION: Pregnancy-associated osteoporosis (PAO) is a rare skeletal condition, which is characterized by a reduction in bone mineral density (BMD) in the course of pregnancy and lactation...
March 29, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29584620/jam3-maintains-leukemia-initiating-cell-self-renewal-through-lrp5-akt-%C3%AE-catenin-ccnd1-signaling
#11
Yaping Zhang, Fangzhen Xia, Xiaoye Liu, Zhuo Yu, Li Xie, Ligen Liu, Chiqi Chen, Haishan Jiang, Xiaoxin Hao, Xiaoxiao He, Feifei Zhang, Hao Gu, Jun Zhu, Haitao Bai, Cheng Cheng Zhang, Guo-Qiang Chen, Junke Zheng
Leukemia-initiating cells (LICs) are responsible for the initiation, development, and relapse of leukemia. The identification of novel therapeutic LIC targets is critical to curing leukemia. In this report, we reveal that junctional adhesion molecule 3 (JAM3) is highly enriched in both mouse and human LICs. Leukemogenesis is almost completely abrogated upon Jam3 deletion during serial transplantations in an MLL-AF9-induced murine acute myeloid leukemia model. In contrast, Jam3 deletion does not affect the functions of mouse hematopoietic stem cells...
March 26, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29579075/effects-of-pharmacologic-sclerostin-inhibition-or-testosterone-administration-on-soleus-muscle-atrophy-in-rodents-after-spinal-cord-injury
#12
Ean G Phillips, Luke A Beggs, Fan Ye, Christine F Conover, Darren T Beck, Dana M Otzel, Payal Ghosh, Anna C F Bassit, Stephen E Borst, Joshua F Yarrow
Sclerostin is a circulating osteocyte-derived glycoprotein that negatively regulates Wnt-signaling after binding the LRP5/LRP6 co-receptors. Pharmacologic sclerostin inhibition produces bone anabolic effects after spinal cord injury (SCI), however, the effects of sclerostin-antibody (Scl-Ab) on muscle morphology remain unknown. In comparison, androgen administration produces bone antiresorptive effects after SCI and some, but not all, studies have reported that testosterone treatment ameliorates skeletal muscle atrophy in this context...
2018: PloS One
https://www.readbyqxmd.com/read/29554480/osteogenesis-potential-of-different-titania-nanotubes-in-oxidative-stress-microenvironment
#13
Yonglin Yu, Xinkun Shen, Zhong Luo, Yan Hu, Menghuan Li, Pingping Ma, Qichun Ran, Liangliang Dai, Ye He, Kaiyong Cai
Oxidative stress is commonly existed in bone degenerative disease (osteoarthritis, osteoporosis etc.) and some antioxidants had great potential to enhance osteogenesis. In this study, we aim to investigate the anti-oxidative properties of various TiO2 nanotubes (TNTs) so to screen the desirable size for improved osteogenesis and reveal the underlying molecular mechanism in vitro. Comparing cellular behaviors under normal and oxidative stress conditions, an interesting conclusion was obtained. In normal microenvironment, small TNTs were beneficial for adhesion and proliferation of osteoblasts, but large TNTs greatly increased osteogenic differentiation...
June 2018: Biomaterials
https://www.readbyqxmd.com/read/29552441/complex-heterozygous-wnt1-mutation-in-severe-recessive-osteogenesis-imperfecta-of-a-chinese-patient
#14
Yanqin Lu, Yunzhang Dai, Yanzhou Wang, Naixiang Zhai, Jian Zhang, Junlong Liu, Xiaoli Yin, Tianyou Li, Xiuzhi Ren, Jinxiang Han
Osteogenesis imperfecta (OI) is a heritable connective tissue disorder with a predominately autosomal-dominant inheritance pattern. Recessive forms of OI are rare and involve many different causative genes. WNT1 mutations were found to cause either autosomal-recessive OI or dominantly inherited early-onset osteoporosis. Here we describe a 32-year-old boy with severe osteopenia and deformity of the extremities. The relative long thumb and ring finger are obvious. We identified a novel combination of complex heterozygous WNT1 mutation of c...
February 2018: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/29541990/a-genome-wide-association-study-on-growth-traits-in-orangespotted-grouper-epinephelus-coioides-with-rad-seq-genotyping
#15
Hui Yu, Xinxin You, Jia Li, Xinhui Zhang, Shuai Zhang, Shoujia Jiang, Xueqiang Lin, Hao-Ran Lin, Zining Meng, Qiong Shi
The orange-spotted grouper, Epinephelus coioides, is one of the most popular fish in China and Southeast Asian countries because of its important economic value. However, molecular mechanism underlying the growth of orange-spotted grouper has never been fully understood. Herein, we performed a genome-wide association study (GWAS) on a natural population of 198 individuals aiming to screen the whole genome of orange-spotted grouper for identification of growth-related loci by restrictionsite associated DNA sequencing...
March 12, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29524275/mutations-in-the-fourth-%C3%AE-propeller-domain-of-lrp4-are-associated-with-isolated-syndactyly-with-fusion-of-the-third-and-fourth-fingers
#16
Rivka Sukenik Halevy, Huan-Chieh Chien, Bo Heinz, Michael J Bamshad, Deborah A Nickerson, Martin Kircher, Nadav Ahituv
Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.D1403H and chr11 g.46893078G>T; p.Q1564K, in LRP4 in a child with isolated bilateral syndactyly of the third and fourth fingers. Each variant was inherited from a different parent and neither parent was affected. Variants in LRP4 have been previously associated with syndactyly in Cenani-Lenz syndactyly syndrome and Sclerosteosis 2, but have not been reported in individuals with isolated syndactyly...
March 10, 2018: Human Mutation
https://www.readbyqxmd.com/read/29511374/transgenic-expression-of-a-venous-malformation-related-mutation-tie2-r849w-significantly-induces-multiple-malformations-of-zebrafish
#17
Zhong Du, Hai-Long Ma, Zhi-Yuan Zhang, Jia-Wei Zheng, Yan-An Wang
A TIE2 mutation causing arginine-to-tryptophan substitution at residue 849 ( TIE2-R849W ) is commonly identified in heredofamilial venous malformation. However, there is no in vivo model to confirm the pathogenic role of TIE2-R849W . Humanized TIE2-R849W plasmid was constructed via PCR-mediated site-directed mutagenesis. After transcription and micro-injection, TIE2-R849W significantly induces multiple malformations in zebrafish: caudal vein plexus (CVP) defect, eye abnormalities, forebrain formation perturbations, and mandibular malformation...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29486968/in-silico-discovery-of-quinoxaline-derivatives-as-novel-lrp5-6-sclerostin-interaction-inhibitors
#18
Jiwon Choi, Kyungro Lee, Myeongmo Kang, Sung-Kil Lim, Kyoung Tai No
The Wnt/β-catenin signaling pathway is a key regulator of bone homeostasis. Sclerostin act as an extracellular inhibitor of canonical Wnt signaling through high-affinity binding to the Wnt co-receptor LRP5/6. Disruption of the interaction between LRP5/6 and sclerostin has been recognized as a therapeutic target for osteoporosis. We identified a quinoxaline moiety as a new small-molecule inhibitor of the LRP5/6-sclerostin interaction through pharmacophore-based virtual screening, docking simulations, and in vitro assays...
April 1, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29458569/recent-progress-of-wnt-pathway-inhibitor-dickkopf-1-in-liver-cancer
#19
Jieping Li, Wenlin Gong, Xiaoxue Li, Ruirong Wan, Fengzhen Mo, Zhenghua Zhang, Panpan Huang, Zixi Hu, Zongqiang Lai, Xiaoling Lu, Yongxiang Zhao
Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Multiple etiologic factors such as virus and environment can lead to HCC. It is a challenge for us to successfully detect early HCC due to the lack of effective characterized and specific biomarkers. However, if the early diagnosis is successfully realized, it provides crucial chance for HCC patients to receive effective treatment as early as possible. Dickkopf-1 (DKK-1) is a secretary glycoprotein, which negatively regulates Wnt pathway through binding to surface receptors LRP5/6 and Kremen 1/2...
August 1, 2018: Journal of Nanoscience and Nanotechnology
https://www.readbyqxmd.com/read/29454962/the-high-bone-mass-phenotype-of-lrp5-mutant-mice-is-not-affected-by-megakaryocyte-depletion
#20
Timur Yorgan, Jean-Pierre David, Michael Amling, Thorsten Schinke
Bone remodeling is a continuously ongoing process mediated by bone-resorbing osteoclasts and bone-forming osteoblasts. One key regulator of bone formation is the putative Wnt co-receptor Lrp5, where activating mutations in the extracellular domain cause increased bone formation in mice and humans. We have previously reported that megakaryocyte numbers are increased the bone marrow of mice carrying a high bone mass mutation (HBM) of Lrp5 (Lrp5G170V ). Since megakaryocytes can promote bone formation, we addressed the question, if the bone remodeling phenotype of Lrp5G170V mice is affected by megakaryocyte depletion...
March 4, 2018: Biochemical and Biophysical Research Communications
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