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Fibroblast Like Synoviocyte

Menglin Fan, Yanan Li, Chunhua Yao, Xiufeng Liu, Xuming Liu, Jihua Liu
Imbalance of Treg/Th17 and chronic synovitis characterized by the recruitment and infiltration of inflammatory cells are the typical features of rheumatoid arthritis (RA). IL-6 promotes the differentiation and function of Th17 cells, which contributes to the imbalance of Treg/Th17 and aggravates lymphocytic infiltration in joints. DC32, a dihydroartemisinin derivative, was found to have anti-inflammatory and immunosuppressive activities in previous study. The aim of this study is to evaluate the effects and mechanisms of DC32 in immunodeficiency and inflammatory infiltration of RA...
October 15, 2018: International Immunopharmacology
Lisa Deloch, Michael Rückert, Rainer Fietkau, Benjamin Frey, Udo S Gaipl
Low-dose radiotherapy (LD-RT) for benign inflammatory and/or bone destructive diseases has been used long. Therefore, mechanistic investigations on cells being present in joints are mostly made in an inflammatory setting. This raises the question whether similar effects of LD-RT are also seen in healthy tissue and thus might cause possible harmful effects. We performed examinations on the functionality and phenotype of key cells within the joint, namely on fibroblast-like synoviocytes (FLS), osteoclasts and osteoblasts, as well as on immune cells...
October 16, 2018: International Journal of Molecular Sciences
Yuqin Zhang, Guohong Yan, Chengtao Sun, Lihong Nan, Xiaoying Wang, Wei Xu, Kedan Chu
Compound 3R-(4'-hydroxyl-3'-O-β-D-glucopyranosyl phenyl)-dihydro isocoumarin (GDC) is a natural isocoumarin, recently isolated from the stems of H. paniculiflorum. However, we know little about the effects of GDC on rheumatoid arthritis (RA). This study aims to investigate the protective effects and potential mechanisms of GDC against LPS-induced inflammation in vitro. Fibroblast-like synoviocytes (FLSs) obtained from synovial tissue of rats were induced by lipopolysaccharide (LPS) and treated with GDC. Cell viability was determined by mitochondrial-respiration-dependent3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay...
October 17, 2018: Inflammation
Huiyi Liang, Bo Peng, Cong Dong, Lixin Liu, Jiaji Mao, Song Wei, Xinlu Wang, Hanshi Xu, Jun Shen, Hai-Quan Mao, Xiaohu Gao, Kam W Leong, Yongming Chen
Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here we show that ~40 nm cationic nanoparticles (cNP) can scavenge cfDNA derived from RA patients and inhibit the activation of primary synovial fluid monocytes and fibroblast-like synoviocytes. Using clinical scoring, micro-CT images, MRI, and histology, we show that intravenous injection of cNP into a CpG-induced mouse model or collagen-induced arthritis rat model can relieve RA symptoms including ankle and tissue swelling, and bone and cartilage damage...
October 16, 2018: Nature Communications
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
Bin Yang, Xiangru Liu, Yongqian Liang, Yue Li
Rheumatoid arthritis fibroblast-like synoviocytes (RAFLS) proliferate abnormally and resist apoptosis. Geldanamycin (GA) and other HSP90 inhibitors have emerged as promising therapeutic agents that inhibited cancer cell growth. In this study, we explored the effects of HSP90 inhibitor, GA, on tumor necrosis factor (TNF)-α-induced proliferation and apoptosis of RAFLS, and the underlying mechanism. Human RAFLS was isolated from the knee joints of patients with RA and subjected to TNF-α treatment in combination of various concentration of GA...
October 10, 2018: Journal of Cellular Biochemistry
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
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
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
Lisa Deloch, Anja Derer, Axel J Hueber, Martin Herrmann, Georg Andreas Schett, Jens Wölfelschneider, Jonas Hahn, Paul-Friedrich Rühle, Willi Stillkrieg, Jana Fuchs, Rainer Fietkau, Benjamin Frey, Udo S Gaipl
Inflammation and bone erosion are central in rheumatoid arthritis (RA). Even though effective medications for control and treatment of RA are available, remission is only seen in a subset of patients. Treatment with low-dose radiotherapy (LD-RT) which has been already successfully used for amelioration of symptoms in benign diseases should be a promising approach to reduce pain, inflammation, and particularly bone erosion in patients with RA. Even though anti-inflammatory effects of LD-RT are already described with non-linear dose response relationships, and pain-reducing effects have been clinically observed, the underlying mechanisms are widely unknown...
2018: Frontiers in Immunology
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
Guo-Hui Yang, Chi Zhang, Nan Wang, Yu Meng, Yi-Sheng Wang
Anacardic acid, which is abundant in nutshell of Anacardium occidentale, has multiple pharmacological activities. In this study, we examined the therapeutic potential of anacardic acid in treating rheumatoid arthritis (RA). We explored the effects of anacardic acid on collagen-induced arthritis (CIA) in mice and on the proliferation and invasion of RA fibroblast-like synoviocytes (RA-FLSs). The underlying molecular mechanism was investigated. Anacardic acid treatment markedly suppressed paw swelling, joint destruction, and arthritis scores in CIA mice...
September 28, 2018: Cytokine
Suping Qin, Dexu Sun, Xiangyang Li, Fanyun Kong, Qian Yu, Hui Hua, Kuiyang Zheng, Renxian Tang
BACKGROUND: Studies have identified that the fibroblast-like synoviocytes (FLS) exhibited tumor-like characteristics and was the key factor in the pathogenesis of Rheumatoid arthritis (RA). GANT61, an antagonist of the sonic hedgehog pathway, has been verified with inhibitory effect on many cancers. Here we investigated the effect of GANT61 on FLS and the development of collagen-induced arthritis (CIA). METHODS: 40 Sprague Dawley (SD) rats were randomly divided into four groups: normal, CIA, CIA+10 mg/kg GANT61 and CIA+20 mg/kg GANT61...
September 26, 2018: Journal of Orthopaedic Science: Official Journal of the Japanese Orthopaedic Association
Leroy Shervington, Ashish Darekar, Murassa Shaikh, Roshini Mathews, Amal Shervington
Introduction and objective: Elevated C-reactive protein is usually a good indicator of rheumatoid arthritis (RA); however, there are limitations that compromise its specificity and therefore there is an urgent need to identify more reliable diagnostic biomarkers to detect early stages of RA. In addition, identifying the correct therapeutic biomarker for the treatment of RA using methotrexate (MTX) would greatly increase the benefits experienced by the patients. Materials and methods: Primary normal synoviocytes human fibroblast-like synoviocytes (HFLS) and its phenotype rheumatic HFLS-RA cells were chosen for this study...
2018: Biomarker Insights
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
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
Rushikesh Sable, Nithya Jambunathan, Sitanshu Singh, Sandeep Pallerla, Konstantin G Kousoulas, Seetharama Jois
Protein-protein interactions (PPI) by homo-, hetero- or oligo-merization in the cellular environment regulate cellular processes. PPI can be inhibited by antibodies, small molecules or peptides, and this inhibition has therapeutic value. A recently developed method, the proximity ligation assay (PLA), provides detection of PPI in the cellular environment. However, most applications using this assay are for proteins expressed in the same cell. We employ PLA for the first time to study PPI of cell surface proteins on two different cells...
September 2018: BioTechniques
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
Xiaoqi Zhang, Hao Feng, Juan Du, Jing Sun, Dongfang Li, Tomoka Hasegawa, Norio Amizuka, Minqi Li
Rheumatoid arthritis (RA) is a commonly occurring autoimmune disease. Its defining pathological characteristic is the excessive proliferation of fibroblast‑like synoviocytes (FLS), which is similar to tumor cells and results in a range of clinical problems. As a commonly used antipyretic, analgesic and anti‑inflammatory drug, aspirin is the first‑line treatment for RA. However, its mechanism of action has not been well explained. The goal is to investigate the biological effects of aspirin on primary RA‑FLS and its underlying mechanisms...
September 17, 2018: International Journal of Molecular Medicine
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
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