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rheumatoid arthritis synovial fibroblast

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https://www.readbyqxmd.com/read/30306514/tackling-pain-associated-with-rheumatoid-arthritis-proton-sensing-receptors
#1
Wei-Hsin Sun, Shih-Ping Dai
Rheumatoid arthritis (RA), characterized by chronic inflammation of synovial joints, is often associated with ongoing pain and increased pain sensitivity. Chronic pain that comes with RA turns independent, essentially becoming its own disease. It could partly explain that a significant number (50%) of RA patients fail to respond to current RA therapies that focus mainly on suppression of joint inflammation. The acute phase of pain seems to associate with joint inflammation in early RA. In established RA, the chronic phase of pain could be linked to inflammatory components of neuron-immune interactions and noninflammatory components...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/30303512/a-three-dimensional-model-to-study-human-synovial-pathology
#2
Mathijs G A Broeren, Claire E J Waterborg, Renske Wiegertjes, Rogier M Thurlings, Marije I Koenders, Peter L E M Van Lent, Peter M Van der Kraan, Fons A J Van de Loo
Therapeutic agents that are used by patients with rheumatic and musculoskeletal diseases were originally developed and tested in animal models, and although retrospective studies show a limited predictive value, it could be explained by the fact that there are no good in vitro alternatives. In this study, we developed a 3-dimensional synovial membrane model made of either human primary synovial cell suspensions or a mix of primary fibroblast-like synoviocytes and CD14+ mononuclear cells. We analyzed the composition of the mature micromasses by immunohistochemical staining and flow cytometry and show that the outer surface forms a lining layer consisting out of fibroblast-like and macrophage-like cells, reflecting the in vivo naïve synovial membrane...
October 9, 2018: ALTEX
https://www.readbyqxmd.com/read/30286793/e2f2-directly-regulates-the-stat1-and-pi3k-akt-nf-%C3%AE%C2%BAb-pathways-to-exacerbate-the-inflammatory-phenotype-in-rheumatoid-arthritis-synovial-fibroblasts-and-mouse-embryonic-fibroblasts
#3
Shiguan Wang, Lin Wang, Changshun Wu, Shui Sun, Ji-Hong Pan
BACKGROUND: Expression of E2F transcription factor 2 (E2F2), a transcription factor related to the cell cycle, is abnormally high in rheumatoid arthritis synovial fibroblasts (RASFs). Deregulated expression of E2F2 leads to abnormal production of proinflammatory cytokines, such as interleukin (IL)-1α, IL-1β, and tumor necrosis factor (TNF)-α in RASFs. However, the underlying mechanism by which E2F2 regulates expression of IL-1α, IL-1β, and TNF-α has not been fully elucidated. This study aimed to elucidate this mechanism and confirm the pathological roles of E2F2 in rheumatoid arthritis (RA)...
October 4, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/30285829/cyld-suppression-enhances-the-pro-inflammatory-effects-and-hyperproliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes-by-enhancing-nf-%C3%AE%C2%BAb-activation
#4
Le-Meng Zhang, Jing-Jing Zhou, Chun-Lei Luo
BACKGROUND: Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) actively drive joint inflammation and degradation by producing inflammatory cytokines and matrix-degrading molecules, making them key factors in the pathogenesis of RA. Cylindromatosis (CYLD) is a tumor suppressor that downregulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation by deubiquitinating NF-κB essential modulator and tumor necrosis factor receptor-associated factors 2 and 6...
October 3, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/30281780/imatinib-inhibits-csf1r-that-stimulates-proliferation-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#5
Xumin Hu, Jianhua Tang, Xuyun Hu, Peng Bao, Jinxin Pan, Yangyi Ou, Weixi Deng, Yuwei Liang
In this study, we aimed to explore the effects of imatinib on the proliferation of rheumatoid arthritis synovial cell (RA-FLS) and inflammatory responses by regulating CSF1R. Differential genes were screened via microarray analysis, followed by being analyzed through WGCNA analysis that included module analysis and cluster analysis. The relationship between imatinib and genes was visualized by Search Tool for the Retrieval of Interacting Genes (STITCH) database. Expressions of mRNA and protein were determined by RT-PCR and western blot, respectively...
October 3, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/30277570/nlrp3-inflammasome-activation-contributes-to-the-pathogenesis-of-rheumatoid-arthritis
#6
C Guo, R Fu, S Wang, Y Huang, X Li, M Zhou, J Zhao, N Yang
Nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) gene polymorphism was reported to be associated with susceptibility, disease activity or anti-tumour necrosis factor (TNF) treatment response in rheumatoid arthritis (RA). However, the roles of NLRP3 inflammasome in the development of RA have not yet been elucidated fully. The present study aimed to study the role of NLRP3 inflammasome in RA. NLRP3 inflammasome activation in synovial tissues from RA and osteoarthritis (OA) patients were assessed by Western blot...
September 16, 2018: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/30272996/critical-role-of-il-1%C3%AE-in-il-1%C3%AE-induced-inflammatory-responses-cooperation-with-nf-%C3%AE%C2%BAbp65-in-transcriptional-regulation
#7
Anil K Singh, Sabrina Fechtner, Mukesh Chourasia, Jerry Sicalo, Salahuddin Ahmed
The IL-1 cytokines are considered among the first family of cytokines that orchestrate acute and chronic inflammatory diseases. Both IL-1β and IL-1α are members of the IL-1 family; however, their distinct roles in the inflammatory processes remain poorly understood. We explored the role of IL-1α in IL-1β-activated signaling pathways causing synovial inflammation in rheumatoid arthritis (RA). Using synovial fibroblasts isolated from RA joints, we found that IL-1β significantly stimulated IL-1α expression, which was selectively inhibited by blocking the NF-κB pathway...
October 1, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30254017/redox-active-trace-metal-induced-release-of-high-mobility-group-box-1-hmgb1-and-inflammatory-cytokines-in-fibroblast-like-synovial-cells-is-toll-like-receptor-4-tlr4-dependent
#8
Asmaa A Alsousi, Orisa J Igwe
Rheumatoid arthritis (RA) is a chronic autoimmune systemic inflammatory disease that is characterized by synovial inflammation and bone erosion. We have investigated the mechanism(s) by which essential trace metals may initiate and propagate inflammatory phenotypes in synovial fibroblasts. We used HIG-82, rabbit fibroblast-like synovial cells (FLS), as a model system for potentially initiating RA through oxidative stress. We used potassium peroxychromate (PPC, Cr+5 ), ferrous chloride (FeCl2, Fe+2 ), and cuprous chloride (CuCl, Cu+ ) trace metal agents as exogenous pro-oxidants...
November 2018: Biochimica et biophysica acta. Molecular basis of disease
https://www.readbyqxmd.com/read/30252968/interactions-between-rheumatoid-arthritis-synovial-fibroblast-migration-and-endothelial-cells
#9
Birgit Zimmermann-Geller, Sina Köppert, Nina Kesel, Rebecca Hasseli, Sebastian Ullrich, Stephanie Lefévre, Klaus Frommer, Thorsten Gehrke, Markus Schönburg, Stephan Rehart, Udo Schumacher, Ulf Müller-Ladner, Elena Neumann
Leukocytes travel within the circulation and enter connective tissues by interactions with endothelium of postcapillary venules mediated by cell adhesion molecules, summarized as leukocyte adhesion cascade. In the SCID-mouse-model, rheumatoid arthritis (RA) synovial fibroblasts (SF) migrated to distant cartilage through the vasculature. Therefore, RASF-adhesion towards endothelial cells (EC) and E- and P- selectins were analyzed. Cell-to-cell-binding assays between SF and EC were performed. Interactions of SF with (TNF-activated) EC or selectins were analyzed in flow-adhesion-assays...
September 25, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/30242542/mir-410-3p-suppresses-cytokine-release-from-fibroblast-like-synoviocytes-by-regulating-nf-%C3%AE%C2%BAb-signaling-in-rheumatoid-arthritis
#10
YueJiao Wang, NeiLi Xu, Shuai Zhao, Ting Jiao, WenYi Fu, LiLi Yang, Ning Zhang
miR-410-3p acts as an oncogene or a tumor suppressor in some malignancies. However, its role in rheumatoid arthritis (RA) is unknown. The study was conducted to investigate the effect of miR-410-3p on the pathogenesis of RA. Real-time RT-PCR was used to determine the mRNA levels of miR-410-3p in synovial tissues and fibroblast-like synoviocytes (FLSs). An ELISA was performed to examine the production levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP)-9. Western blotting was conducted to determine the protein levels of IκB-α, p-IκBα, p65, and p-p65...
September 21, 2018: Inflammation
https://www.readbyqxmd.com/read/30236152/1-25-oh-2-d-3-and-dexamethasone-additively-suppress-synovial-fibroblast-activation-by-ccr6-t-helper-memory-cells-and-enhance-the-effect-of-tumor-necrosis-factor-alpha-blockade
#11
Wendy Dankers, Claudia González-Leal, Nadine Davelaar, Patrick S Asmawidjaja, Adriana M C Mus, Johanna M W Hazes, Edgar M Colin, Erik Lubberts
BACKGROUND: Despite recent improvements in the treatment of rheumatoid arthritis (RA), an insufficient treatment response and the development of treatment resistance in many patients illustrates the need for new therapeutic strategies. Chronic synovial inflammation could be suppressed by targeting RA synovial fibroblast (RASF) activation by, for example, interleukin (IL)-17A-producing CCR6+ T helper memory (memTh) cells. Here, we modulated this interaction by combining the active vitamin D metabolite 1,25(OH)2 D3 with dexamethasone (DEX) and explored the potential therapeutic applications...
September 20, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/30232236/tanshinone-iia-promotes-the-apoptosis-of-fibroblast-like-synoviocytes-in-rheumatoid-arthritis-by-up-regulating-lncrna-gas5
#12
Guoqing Li, Ying Liu, Fanru Meng, Zhongbin Xia, Xia Wu, Yuxuan Fang, Chunwang Zhang, Dan Liu
Rheumatoid arthritis (RA) is a common chronic autoimmune joint disease characteristic of elevated proliferation and infiltration of fibroblast-like synoviocytes (FLS). Here, we aimed to explore the mechanisms of the Tanshinone IIA (Tan IIA)-induced apoptosis of FLS from patients with RA (termed RAFLS). Cell Counting Kit-8 (CCK-8) assay and Annexin V staining revealed that RAFLS viability decreased and apoptosis increased after Tan IIA treatment. Long non-coding RNA (lncRNA) GAS5 expression was significantly decreased in the synovial tissues and RAFLS, while Tan IIA treatment resulted in an up-regulation of GAS5...
October 31, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/30227223/circadian-rhythms-and-rheumatoid-arthritis
#13
Cutolo Maurizio
Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of proinflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night...
September 15, 2018: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/30226571/3-5-di-c-%C3%AE-d-glucopyranosyl-phloroacetophenone-a-major-component-of-melicope-ptelefolia-suppresses-fibroblast-activation-and-alleviates-arthritis-in-a-mouse-model-potential-therapeutics-for-rheumatoid-arthritis
#14
Hyun Jong Kim, Ji Hyun Choi, Jung-Hwan Hwang, Kyong-Shim Kim, Jung-Ran Noh, Dong-Hee Choi, Sung Je Moon, Hyun-Yong Kim, Sang-Woo Kim, Sangho Choi, Sang Mi Eum, Tran The Bach, Jaerang Rho, Ju Yong Lee, Jung Geun Park, Sei-Ryang Oh, Chul-Ho Lee, Won Keun Oh, Yong-Hoon Kim
Melicope ptelefolia has been traditionally used to treat rheumatism and fever. The present study aimed to investigate the therapeutic effect of 3,5‑di‑C‑β‑D‑glucopyranosyl phloroacetophenone (βGP), a main component of M. ptelefolia, on rheumatoid arthritis (RA). A model of collagen‑induced arthritis (CIA) was established in mice using the RAW 264.7 murine macrophage cell line and mouse embryonic fibroblasts (MEFs). The clinical scores of arthritis, swelling, histopathological findings, and micro‑computed tomography in CIA mouse paws were assessed...
November 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30224512/therapeutic-potential-of-mesenchymal-cell-derived-mirna-150-5p-expressing-exosomes-in-rheumatoid-arthritis-mediated-by-the-modulation-of-mmp14-and-vegf
#15
Zhe Chen, Hanqi Wang, Yang Xia, Fuhua Yan, Yong Lu
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial tissue inflammation and joint destruction associated with the activation of angiogenesis. Exosomes, which play a role in cell-to-cell communication as carriers of genetic information, transfer microRNAs (miRNAs or miRs) between cells and have been studied as delivery vehicles for therapeutic molecules. The aim of the current study was to investigate the therapeutic effect of mesenchymal stem cell (MSC)-derived miR-150-5p exosomes on joint destruction in RA...
October 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30198906/long-noncoding-rna-lerfs-negatively-regulates-rheumatoid-synovial-aggression-and-proliferation
#16
Yaoyao Zou, Siqi Xu, Youjun Xiao, Qian Qiu, Maohua Shi, Jingnan Wang, Liuqin Liang, Zhongping Zhan, Xiuyan Yang, Nancy Olsen, Song Guo Zheng, Hanshi Xu
Fibroblast-like synoviocytes (FLSs) are critical to synovial aggression and joint destruction in rheumatoid arthritis (RA). The role of long noncoding RNAs (lncRNAs) in RA is largely unknown. Here, we identified a lncRNA, LERFS (lowly expressed in rheumatoid fibroblast-like synoviocytes), that negatively regulates the migration, invasion, and proliferation of FLSs through interaction with heterogeneous nuclear ribonucleoprotein Q (hnRNP Q). Under healthy conditions, by binding to the mRNA of RhoA, Rac1, and CDC42 - the small GTPase proteins that control the motility and proliferation of FLSs - the LERFS-hnRNP Q complex decreased the stability or translation of target mRNAs and downregulated their protein levels...
October 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/30167920/mirna-126-expression-inhibits-il-23r-mediated-tnf-%C3%AE-or-ifn-%C3%AE-production-in-fibroblast-like-synoviocytes-in-a-mice-model-of-collagen-induced-rheumatoid-arthritis
#17
Jie Gao, Ruina Kong, Xiaoli Zhou, Lianmei Ji, Ju Zhang, Dongbao Zhao
Both miR-126 and IL-23R affect rheumatoid arthritis (RA) procession. This study aimed to investigate the association of miR-126 and IL-23R and the possible modulation of miR-126 to RA pathogenesis. Serum, synovial tissue and synovial fluid were collected from patients with RA, and expression of miR-126, IL-23R, TNF-α and IFN-γ were detected. Fibroblast-like synoviocytes (FLS) was established using a collagen-induced arthritis mice model. The expression of miR-126 was manual intervened using pro-miR-126 and anti-miR-126 encoding lentivirus plasmids, or miR-126 agonists and corresponding negative controls...
August 24, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/30166712/pathogenesis-of-rheumatoid-arthritis-the-intersection-of-genetics-and-epigenetics
#18
Gary S Firestein
Rheumatoid arthritis is a synovial inflammatory disease marked by joint infiltration by immune cells and damage to the extracellular matrix. Although genetics plays a critical role in heritability and its pathogenesis, the relative lack of disease concordance in identical twins suggests that noncoding influences can affect risk and severity. Environmental stress, which can be reflected in the genome as altered epigenetic marks, also contributes to gene regulation and contributes to disease mechanisms. Studies on DNA methylation suggest that synovial cells, most notably fibroblast-like synoviocytes, are imprinted in rheumatoid arthritis with epigenetic marks and subsequently assume an aggressive phenotype...
2018: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/30157923/osteogenic-differentiation-of-fibroblast-like-synovial-cells-in-rheumatoid-arthritis-is-induced-by-microrna-218-through-a-robo-slit-pathway
#19
Naoki Iwamoto, Shoichi Fukui, Ayuko Takatani, Toshimasa Shimizu, Masataka Umeda, Ayako Nishino, Takashi Igawa, Tomohiro Koga, Shin-Ya Kawashiri, Kunihiro Ichinose, Mami Tmai, Hideki Nakamura, Tomoki Origuchi, Ko Chiba, Makoto Osaki, Astrid Jüngel, Steffen Gay, Atsushi Kawakami
BACKGROUND: Fibroblast-like synovial cells (FLS) have multilineage differentiation potential including osteoblasts. We aimed to investigate the role of microRNAs during the osteogenic differentiation of rheumatoid arthritis (RA)-FLS. METHODS: RA-FLS were differentiated in osteogenic medium for 21 days. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) staining and Alizarin Red staining. MicroRNA (miRNA) array analysis was performed to investigate the differentially expressed miRNAs during osteogenic differentiation...
August 29, 2018: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/30150656/endogenous-galectin-9-suppresses-apoptosis-in-human-rheumatoid-arthritis-synovial-fibroblasts
#20
Mark J Pearson, Magdalena A Bik, Caroline Ospelt, Amy J Naylor, Corinna Wehmeyer, Simon W Jones, Christopher D Buckley, Steffen Gay, Andrew Filer, Janet M Lord
Galectin-9 (Gal9) has been postulated to have anti-inflammatory properties based on the ability of exogenous Gal9 to induce apoptosis in synovial fibroblasts in animal models of rheumatoid arthritis (RA). Here we aimed to assess the potential role of endogenous Galectins, including Gal9, in the inflammatory pathology of the RA synovium in humans. Firstly expression of Galectins 1-9 was determined in synovial fibroblasts (RASF) and dermal fibroblasts (DF) isolated from RA patients, the latter representing a non-inflamed site...
August 27, 2018: Scientific Reports
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