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Rheumatoid arthritis;synovial

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https://www.readbyqxmd.com/read/28225071/resolution-of-tlr2-induced-inflammation-through-manipulation-of-metabolic-pathways-in-rheumatoid-arthritis
#1
Trudy McGarry, Monika Biniecka, Wei Gao, Deborah Cluxton, Mary Canavan, Siobhan Wade, Sarah Wade, Lorna Gallagher, Carl Orr, Douglas J Veale, Ursula Fearon
During inflammation, immune cells activated by toll-like receptors (TLRs) have the ability to undergo a bioenergetic switch towards glycolysis in a manner similar to that observed in tumour cells. While TLRs have been implicated in the pathogenesis of rheumatoid arthritis (RA), their role in regulating cellular metabolism in synovial cells, however, is still unknown. In this study, we investigated the effect of TLR2-activation on mitochondrial function and bioenergetics in primary RA-synovial fibroblast cells (RASFC), and further determined the role of glycolytic blockade on TLR2-induced inflammation in RASFC using glycolytic inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO)...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28220341/adenovirus-mediated-small-interfering-rna-targeting-tak1-ameliorates-joint-inflammation-with-collagen-induced-arthritis-in-mice
#2
Xinjing Luo, Yongfeng Chen, Guoju Lv, Zhidong Zhou, Jie Chen, Xuanrong Mo, Jiangwen Xie
Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice...
February 21, 2017: Inflammation
https://www.readbyqxmd.com/read/28212115/predictor-of-hand-radiological-progression-in-patients-with-rheumatoid-arthritis-receiving-tnf-antagonist-therapy-by-change-in-grayscale-synovitis-a-preliminary-study
#3
Ying-Chou Chen, Fu-Mei Su, Shih-Wei Hsu, Jia-Feng Chen, Tien-Tsai Cheng, Han-Ming Lai, Wen-Chan Chiu
OBJECTIVES: This prospective study aimed to compare synovial ultrasound scores to conventional measures (DAS28, CRP levels) in predicting radiographic progression in patients with rheumatoid arthritis under TNF antagonist therapy. METHODS: Patients with RA who received TNF antagonist therapy were enrolled, all of whom underwent clinical, laboratory, and ultrasonographic assessments with grayscale and power Doppler assessments of bilateral elbows (anterior and posterior recess), wrists (dorsal, palmar, and ulnar aspects), second and third MCP joints (dorsal and palmar recess), and PIP II and III (dorsal and palmar) at baseline and at 1, 3 months...
February 17, 2017: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
https://www.readbyqxmd.com/read/28199970/three-single-nucleotide-polymorphisms-of-tnfaip3-gene-increase-the-risk-of-rheumatoid-arthritis
#4
Nan Shen, Yuan Ruan, Yajun Lu, Xuefeng Jiang, Huiqing Sun, Gongming Gao, Luming Nong, Kewei Ren
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic destructive inflammation in synovial joints. To date, many studies explored the associations between tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene rs6920220, rs2230926, and rs5029937 polymorphisms and the risk of rheumatoid arthritis (RA), but with contradictory results. We therefore conducted a comprehensive meta-analysis to address the associations. We searched in the databases of PubMed and Embase. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Stata 11...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28192374/transcription-factor-nfat5-promotes-macrophage-survival-in-rheumatoid-arthritis
#5
Susanna Choi, Sungyong You, Donghyun Kim, Soo Youn Choi, H Moo Kwon, Hyun-Sook Kim, Daehee Hwang, Yune-Jung Park, Chul-Soo Cho, Wan-Uk Kim
Defective apoptotic death of activated macrophages has been implicated in the pathogenesis of rheumatoid arthritis (RA). However, the molecular signatures defining apoptotic resistance of RA macrophages are not fully understood. Here, global transcriptome profiling of RA macrophages revealed that the osmoprotective transcription factor nuclear factor of activated T cells 5 (NFAT5) critically regulates diverse pathologic processes in synovial macrophages including the cell cycle, apoptosis, and proliferation...
February 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28187781/priming-in-response-to-pro-inflammatory-cytokines-is-a-feature-of-adult-synovial-but-not-dermal-fibroblasts
#6
Thomas Crowley, John D O'Neil, Holly Adams, Andrew M Thomas, Andrew Filer, Christopher D Buckley, Andrew R Clark
BACKGROUND: It has been hypothesized that chronic inflammatory diseases such as rheumatoid arthritis (RA) may be caused by a failure of negative feedback mechanisms. This study sought to examine negative feedback mechanisms in fibroblast-like synoviocytes (FLS), one of the most abundant cell types in the joint. We hypothesized that prior exposure of healthy FLS to an inflammatory stimulus would attenuate their responses to a second inflammatory stimulus, in the same way that negative feedback mechanisms desensitize macrophages to repeated stimulation by lipopolysaccharide...
February 10, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28187436/dishevelled2-promotes-apoptosis-and-inhibits-inflammatory-cytokine-secretion-in-rheumatoid-arthritis-fibroblast-like-synoviocytes-through-crosstalk-with-the-nf-%C3%AE%C2%BAb-pathway
#7
Xing Zhen Liu, Jie Fan, Ke Qi, Shu Peng Liu, Wei Dong Xu, Ying Gao, Xiao Dan Gu, Jia Li, Chen Guang Bai, Ye Qing Shi, Lan Ling Zhang, Dong Bao Zhao
Dishevelled (Dvl) not only links the canonical Wnt and non-canonical Wnt pathways but can also crosstalk with other pathways. As there is no systematic study to date on Dvl in rheumatoid arthritis (RA), we explored the impact of Dvl2 on proliferation and inflammatory cytokine secretion in RA fibroblast-like synoviocytes (FLSs). Expression of Dvl2 in RA synovial tissue and RA-FLSs was measured. Dvl2 was overexpressed in collagen-induced arthritis rats and human RA-FLSs,. the apoptosis and secretion of inflammatory cytokines were observed...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28167299/1-25-oh-2d3-and-calcipotriol-its-hypocalcemic-analog-exert-a-long-lasting-anti-inflammatory-and-anti-proliferative-effect-in-synoviocytes-cultured-from-patients-with-rheumatoid-arthritis-and-osteoarthritis
#8
Johanna A Huhtakangas, Johanna Veijola, Sanna Turunen, Anna Karjalainen, Maarit Valkealahti, Tomi Nousiainen, Susanna Yli-Luukko, Olli Vuolteenaho, Petri Lehenkari
OBJECTIVES: We investigated the effects of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3), i.e. biologically active vitamin D and calcipotriol, a vitamin D analogue, on growth and secretion of inflammatory mediators in synovial stromal cells (SSC) of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). METHODS: Synovial stromal cells (SSC) isolated during knee prosthesis surgery from four patients with RA and four with OA were exposed to 1,25(OH)2D3 or calcipotriol with or without stimulation of cells with IL-1β or TNF-α...
February 3, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28166724/association-between-il-17-and-iga-in-the-joints-of-patients-with-inflammatory-arthropathies
#9
Ricardo Javier Eliçabe, Juan Eduardo Silva, Mabel Noemí Dave, María Gabriela Lacoste, Héctor Tamashiro, Rodrigo Blas, Alicia Munarriz, Gabriel Adrián Rabinovich, María Silvia Di Genaro
BACKGROUND: Hyperactive secretion and pathogenic effects of interleukin (IL)-17 and IgA have been detected in different arthropathies. Recent evidence has revealed that TH17 cytokines regulate mucosal IgA secretion. However, it is unknown whether and how IL-17 mediates synovial IgA production. Here we aim to investigate the connection of synovial IL-17 with IgA production in the joint. In this study we included synovial fluids (SF) from patients with rheumatoid arthritis (RA; n = 66), spondyloarthritis (SpA; n = 18) and osteoarthritis (OA; n = 36)...
February 6, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28160411/active-synovitis-in-the-presence-of-osteitis-predicts-residual-synovitis-in-patients-with-rheumatoid-arthritis-with-a-clinical-response-to-treatment
#10
Jun Fukae, Kazuhide Tanimura, Masato Isobe, Akemi Kitano, Mihoko Henmi, Maria Nakai, Yuko Aoki, Fumihiko Sakamoto, Akihiro Narita, Takeya Ito, Akio Mitsuzaki, Megumi Matsuhashi, Masato Shimizu, Tamotsu Kamishima, Tatsuya Atsumi, Takao Koike
AIM: To clarify the relationship between active synovitis/osteitis and subsequent residual synovitis (R-synovitis) in patients with rheumatoid arthritis (RA). METHODS: Three hundred and twenty finger joints of 16 patients with active RA at baseline (Disease Activity Score with 28 joints - erythrocyte sedimentation rate > 3.2) who subsequently achieved clinical low disease activity or remission afterwards were analyzed. Synovial vascularity (SV) was assessed according to a semi-quantitative ultrasound score (grades 0-3)...
February 3, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28148700/the-omeract-ultrasound-group-a-report-from-the-omeract-2016-meeting-and-perspectives
#11
Lene Terslev, Annamaria Iagnocco, George A W Bruyn, Esperanza Naredo, Jelena Vojinovic, Paz Collado, Nemanja Damjanov, Andrew Filer, Georgios Filippou, Stephanie Finzel, Frederique Gandjbakhch, Kei Ikeda, Helen I Keen, Marion C Kortekaas, Silvia Magni-Manzoni, Sarah Ohrndorf, Carlos Pineda, Viviana Ravagnani, Bethan Richards, Ilfita Sahbudin, Wolfgang A Schmidt, Heidi J Siddle, Maria S Stoenoiu, Marcin Szkudlarek, Nikolay Tzaribachev, Maria-Antonietta D'Agostino
OBJECTIVE: To provide an update from the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group on the progress for defining ultrasound (US) minimal disease activity threshold at joint level in rheumatoid arthritis (RA) and for standardization of US application in juvenile idiopathic arthritis (JIA). METHODS: For minimal disease activity, healthy controls (HC) and patients with early arthritis (EA) who were naive to disease-modifying antirheumatic drugs were recruited from 2 centers...
February 1, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28143790/association-of-il17a-and-il17f-genes-with-rheumatoid-arthritis-disease-and-the-impact-of-genetic-polymorphisms-on-response-to-treatment
#12
Ouled Salah Marwa, Tizaoui Kalthoum, Kaabachi Wajih, Hamzaoui Kamel
BACKGROUND: Previous studies have reported an association between polymorphisms in Il17A and IL17F genes and the prevalence of rheumatoid arthritis (RA) in Caucasian populations. The aim of the current study was to investigate that polymorphisms in both genes may affect RA susceptibility in the Tunisian population and to study the relation between serum IL-17 levels and synovial fluid (SF) levels and risk in RA patients. We suggested also that these polymorphisms may influence response to treatment in Tunisian RA patients...
March 2017: Immunology Letters
https://www.readbyqxmd.com/read/28132045/the-role-of-t-regulatory-and-th17-cells-in-the-pathogenesis-of-rheumatoid-arthritis-review
#13
N Kikodze, I Pantsulaia, T Chikovani
Chronic inflammation of joints of autoimmune origin - rheumatoid arthritis - develops due to deplorable coincidence of genetic, immune and environmental factors. Th17 cells are considered as the main effector cells in the pathogenesis of rheumatoid arthritis. Analysis of many reports clarify positive correlation between the frequencies of circulating Th17 cells, serum levels of IL-17A and IL-23, synovial IL-17 and disease activity. Autoreactive Th clone response is regulated by the certain population of suppressor cells - T regulatory cells (Tregs)...
December 2016: Georgian Medical News
https://www.readbyqxmd.com/read/28129626/mir-650-inhibits-proliferation-migration-and-invasion-of-rheumatoid-arthritis-synovial-fibroblasts-by-targeting-akt2
#14
Xiaoyan Xu, Haiyan Chen, Qin Zhang, Jin Xu, Qing Shi, Meimei Wang
BACKGROUND AND OBJECTIVES: This study was aimed to investigate the effects of miR-650 on the proliferation, migration, invasion and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Synovial tissue samples were collected from 16 rheumatoid arthritis (RA) patients and 13 patients with joint trauma undergoing joint replacement surgery. The RASFs were isolated and cultured. MiR-650 and AKT2 expressions in both synovial tissues and cells were detected using the quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC)...
January 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28128853/pad4-inhibition-is-sufficient-for-the-amelioration-of-collagen-induced-arthritis
#15
Van C Willis, Nirmal K Banda, Kristen N Cordova, Piyanka E Chandra, William H Robinson, David C Cooper, Dave Lugo, Gaurav Mehta, Simon Taylor, Paul P Tak, Rab K Prinjha, Huw D Lewis, V Michael Holers
Citrullination of joint proteins by the PAD family of enzymes is increasingly recognized as a key process in the pathogenesis of rheumatoid arthritis. This present study was undertaken to explore the efficacy of a novel PAD4-selective inhibitor, GSK199, in the murine collagen-induced arthritis model of rheumatoid arthritis. Mice were dosed daily from the time of collagen immunization with GSK199. Efficacy was assessed against a wide range of endpoints, including clinical disease scores, joint histology and immunohistochemistry, serum and joint citrulline levels, and quantification of synovial autoantibodies using a proteomic array containing joint peptides...
January 27, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28121199/functional-analysis-of-choline-transporters-in-rheumatoid-arthritis-synovial-fibroblasts
#16
Masayuki Seki, Yuiko Kawai, Chikanao Ishii, Tsuyoshi Yamanaka, Masato Odawara, Masato Inazu
OBJECTIVES: In this study, we examined the functional characteristics of choline uptake and sought to identify the transporters in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: The expression of choline transporters was evaluated by quantitative real-time PCR, western blotting, and immunocytochemistry. Time course, Na(+)-dependency, and kinetics of [(3)H]choline uptake were investigated. Effects of cationic drugs on the uptake of [(3)H]choline, cell viability, and caspase-3/7 activity were also examined...
February 1, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28120218/platelet-rich-plasma-inhibits-inflammatory-factors-and-represses-rheumatoid-fibroblast-like-synoviocytes-in-rheumatoid-arthritis
#17
Shichao Tong, Ji Liu, Changqing Zhang
Rheumatoid arthritis (RA) is a chronic disease affecting daily life of numerous patients, and uncontrolled proliferation of synovial fibroblasts plays vital role during the pathology of RA. Platelet-rich plasma (PRP), widely used in tissue regeneration and pain management, is rarely studied in RA. This study aims to investigate the effect of PRP on synovial fibroblasts during RA. Rheumatoid fibroblast-like synoviocyte MH7A cells were stimulated by lipopolysaccharide (LPS) to simulate RA conditions and treated with PRP, after that the concentration of inflammatory factors interleukin (IL) 1β, tumor necrosis factor alpha (TNFα) and IL6 in the supernatant of culture medium was quantified by ELISA...
January 24, 2017: Clinical and Experimental Medicine
https://www.readbyqxmd.com/read/28119289/synovial-features-of-patients-with-rheumatoid-arthritis-and-psoriatic-arthritis-in-clinical-and-ultrasound-remission-differ-under-anti-tnf-therapy-a-clue-to-interpret-different-chances-of-relapse-after-clinical-remission
#18
Stefano Alivernini, Barbara Tolusso, Luca Petricca, Laura Bui, Gabriele Di Sante, Giusy Peluso, Roberta Benvenuto, Anna Laura Fedele, Franco Federico, Gianfranco Ferraccioli, Elisa Gremese
OBJECTIVE: To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. METHODS: Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6<DAS<2.4 for at least 6 months) and patients with PsA in remission (n=18) (DAS<1...
January 24, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28118944/microrna-155-contributes-to-enhanced-resistance-to-apoptosis-in-monocytes-from-patients-with-rheumatoid-arthritis
#19
Megha Rajasekhar, Anton M Olsson, Kathryn J A Steel, Mirella Georgouli, Ushan Ranasinghe, Christine Brender Read, Klaus S Frederiksen, Leonie S Taams
Monocytes and macrophages are key mediators of inflammation in rheumatoid arthritis (RA). Their persistence at the inflammatory site is likely to contribute to immunopathology. We sought to characterise one mechanism by which persistence may be achieved: resistance to apoptosis and the role of mir-155 in this process. CD14+ monocytes from peripheral blood (PBM) and synovial fluid (SFM) of RA patients were found to be resistant to spontaneous apoptosis relative to PBM from healthy control (HC) individuals. RA SFM were also resistant to anti-Fas-mediated apoptosis and displayed a gene expression profile distinct from HC and RA PBM populations...
January 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28118534/disease-associated-anti-citrullinated-protein-memory-b-cells-in-rheumatoid-arthritis-persist-in-clinical-remission
#20
Adam J Pelzek, Caroline Grönwall, Pamela Rosenthal, Jeffrey D Greenberg, Mandy McGeachy, Larry Moreland, William F C Rigby, Gregg J Silverman
OBJECTIVE: In RA, autoreactive B cells are pathogenic drivers and sources of anti-citrullinated protein antibodies (ACPA) that serve as a diagnostic biomarker and predictor of worse long-term prognosis. Yet the immunobiologic significance of persistent ACPA production at a cellular level is poorly understood. METHODS: In a cross-sectional study of RA patients, we investigated for the presence of continued defects in immune homeostasis as a function of disease activity...
January 24, 2017: Arthritis & Rheumatology
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