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rheumatoid arthritis synovial fibroblast

Yosuke Takamura, Wataru Aoki, Atsushi Satomura, Seiji Shibasaki, Mitsuyoshi Ueda
Rheumatoid arthritis (RA) is an autoimmune disease that causes the chronic inflammation of the joints. Intercellular communication containing synovial fibroblasts seems to play a major role in RA pathogenesis. In this study, to better understand intercellular communication related to RA pathogenesis, we identified exosomal microRNAs (miRNAs) derived from synovial fibroblasts. Exosomes were collected from an RA synovial fibroblast (RASF) cell line, namely, MH7A, with or without stimulation by tumor necrosis factor alpha (TNF-α)...
2018: PloS One
Dorota Trzybulska, Anna Olewicz-Gawlik, Jan Sikora, Magdalena Frydrychowicz, Agata Kolecka-Bednarczyk, Mariusz Kaczmarek, Pawel Hrycaj
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destructive changes in peripheral joints and their irreversible deformity. The influx of chemoattractant-mediated inflammatory cells to the joints is one of the main features of RA. OBJECTIVES: The aim of this study was to investigate the effect of a knockdown of caveolin-1 (CAV1), a known regulator of multiple cell signaling pathways, on chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) expression in synovial fluid-derived fibroblast-like synoviocytes (sfd-FLSs) obtained from patients with RA...
August 6, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Jong Y Lee, Geum J Kim, Jin K Choi, Young-Ae Choi, Na-Hee Jeong, Pil-Hoon Park, Hyukjae Choi, Sang-Hyun Kim
Rheumatoid arthritis (RA) is a progressive autoimmune disease specific to synovial joints; it causes joint damage and other systemic abnormalities, thereby leading to physical disability and early mortality. Marine sponge-derived fungi, Pestalotiopsis sp., secrete immunosuppressive compounds in the culture broth. In the present study, we isolated 4-(hydroxymethyl)catechol (4-HMC) from these fungal species, and evaluated its anti-RA effects using a murine collagen-induced arthritis model and tumor necrosis factor-α-stimulated human RA synovial fibroblasts...
2018: Frontiers in Pharmacology
Hiroyuki Nakamura, Sanae Shimamura, Shinsuke Yasuda, Michihito Kono, Michihiro Kono, Yuichiro Fujieda, Masaru Kato, Kenji Oku, Toshiyuki Bohgaki, Tomohiro Shimizu, Norimasa Iwasaki, Tatsuya Atsumi
OBJECTIVES: Rheumatoid arthritis (RA) is an autoimmune polyarthritis, in which fibroblast-like synoviocytes (FLS) play a key role in cartilage and bone destruction through tumour-like proliferation and invasiveness. Considering still unsatisfactory remission rate in RA even under treatment with biological disease-modifying antirheumatic drugs, novel therapeutic strategy for treatment-resistant RA is still awaited. In this study, we analysed the expression and function of Ras guanine nucleotide-releasing proteins (RASGRPs), guanine exchange factors for small GTPase Ras, in FLS as a potential therapeutic target for RA...
August 3, 2018: Annals of the Rheumatic Diseases
Yosra Bedoui, Claude Giry, Marie-Christine Jaffar-Bandjee, Jimmy Selambarom, Pascale Guiraud, Philippe Gasque
Chikungunya virus (CHIKV) is a mosquito-transmitted RNA alphavirus causing major outbreaks of infectious chronic inflammatory rheumatisms (CIR). Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug has been used successfully to treat patients suffering from rheumatoid-like arthritis post-CHIK but its immunomodulatory activity in the context of viral persistence has been a matter of concerns. We herein used a model of primary human synovial fibroblasts (HSF) and the synthetic molecule polyriboinosinic:polyribocytidylic acid (PIC) to mimic chronic infectious settings in the joints of CHIKV infected patients...
August 3, 2018: PLoS Neglected Tropical Diseases
Weiqian Chen, Julie Wang, Zhenjian Xu, Feng Huang, Wenbin Qian, Jilin Ma, Hwa Bok Wee, Gregory S Lewis, Rayford R June, Peter H Schafer, Jin Lin, Song Guo Zheng
Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4+ Foxp3+ regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes...
2018: Frontiers in Immunology
Sho Ishii, Takeo Isozaki, Hidekazu Furuya, Hiroko Takeuchi, Yumi Tsubokura, Katsunori Inagaki, Tsuyoshi Kasama
BACKGROUND: To examine the expression of ADAM-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte adhesion to RA fibroblast-like synoviocytes (FLSs). METHODS: ADAM-17 expression was measured by enzyme-linked immunosorbent assays (ELISAs) in serum from normal (NL) subjects, osteoarthritis (OA) patients, and RA patients. We also analyzed the correlation between ADAM-17 and disease activity score 28 (DAS28) in RA. To determine expression of ADAM-17 in RA synovial tissues (STs) and RA FLS, we performed immunofluorescence analyses...
August 2, 2018: Arthritis Research & Therapy
Marta F Bustamante, Patricia G Oliveira, Ricard Garcia-Carbonell, Adam P Croft, Jeff M Smith, Ramon L Serrano, Elsa Sanchez-Lopez, Xiao Liu, Tatiana Kisseleva, Nissim Hay, Christopher D Buckley, Gary S Firestein, Anne N Murphy, Shigeki Miyamoto, Monica Guma
OBJECTIVES: Recent studies indicate that glucose metabolism is altered in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Hexokinases (HKs) catalyse the first step in glucose metabolism, and HK2 constitutes the principal HK inducible isoform. We hypothesise that HK2 contributes to the synovial lining hypertrophy and plays a critical role in bone and cartilage damage. METHODS: HK1 and HK2 expression were determined in RA and osteoarthritis (OA) synovial tissue by immunohistochemistry...
July 30, 2018: Annals of the Rheumatic Diseases
J Li, Q Song, L Shao, L-L Zhang, X-H Guo, Y-J Mao
OBJECTIVE: To investigate the impact of miR-124Aa on the proliferation, invasion and cytokine excretion of rheumatoid arthritis synovial fibroblasts (RASFs) in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: RASFs were separated for in-vitro culture, and transfected using lipidosome that connected with chemically synthesized miR-124a mimic or miR-124a inhibitor. Then, MTT, transwell chamber, and flow-cytometry were used to detect the impact on the proliferation, invasion, and apoptosis of RASFs; RT-PCR and Western-blotting were employed to measure the effect of miR-124a on the expressions of matrixmetalloproteinase3/13 (MMP3/13) and interleukin1β (IL-1β) of RASFs...
July 2018: European Review for Medical and Pharmacological Sciences
Teresina Laragione, Max Brenner, Amit Lahiri, Erjing Gao, Carolyn Harris, Percio S Gulko
OBJECTIVES: While new treatments for rheumatoid arthritis (RA) have markedly improved disease control by targeting immune/inflammatory pathways, current treatments rarely induce remission, underscoring the need for therapies that target other aspects of the disease. Little is known about the regulation of disease severity and joint damage, which are major predictors of disease outcome, and might be better or complementary targets for therapy. In this study, we aimed to discover and characterise a new arthritis severity gene...
July 26, 2018: Annals of the Rheumatic Diseases
Wei Zhang, Le Chen, Yi Jiang, Yonghui Shen
BACKGROUND We studied the expression and effect of miR-26a-5p in synovial fibroblast in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS The synovial tissues of 55 RA patients with total knee arthroplasty performed from January 2016 to December 2016 were collected as the RA group, and 62 patients without RA history amputation or total knee arthroplasty served as the control group. The expressions of miR-26a-5p and Smad 1 mRNA in synovial fibroblast in patients with RA were detected by qPCR; The expression of Smad 1 and TGF-β1 protein in synovial tissue or synovial fibroblasts was detected by immunoblotting...
July 26, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Elisa Corsiero, Lucas Jagemann, Mauro Perretti, Costantino Pitzalis, Michele Bombardieri
Rheumatoid arthritis (RA) is characterized by formation of synovial ectopic lymphoid structures (ELS) supporting B cell autoreactivity toward locally generated citrullinated (cit) antigens, including those contained in neutrophil extracellular traps (NETs). However, only a minority of RA-rmAbs from B cells isolated from ELS+ RA tissues react against NETs. Thus, alternative cellular sources of other potential autoantigens targeted by locally differentiated B cells remain undefined. RA fibroblast-like synoviocytes (FLS) have been implicated in the release of RA-associated autoantigens...
July 25, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Kerstin Klein, Masaru Kato, Mojca Frank-Bertoncelj, Christoph Kolling, Adrian Ciurea, Steffen Gay, Caroline Ospelt
Targeting epigenetic reader proteins by small molecule inhibitors represents a new therapeutic concept in autoimmune diseases such as rheumatoid arthritis (RA). Although inhibitors targeting bromodomain protein 1 (BRD1) are in development, the function of BRD1 has hardly been studied. We investigated the therapeutic potential of BRD1 inhibition in joint-resident cells in RA, synovial fibroblasts (SF) and macrophages. The proliferation of SF was decreased upon BRD1 silencing, accompanied by the downregulation of genes involved in cell cycle regulation...
July 24, 2018: Scientific Reports
Noriko Komatsu, Hiroshi Takayanagi
The immune and bone systems maintain homeostasis by closely interacting with each other. Rheumatoid arthritis is a pathological consequence of their interplay, since activated T cell immune responses result in osteoclast-mediated bone erosion. An imbalance between Foxp3+ Treg and Th17 cells is often linked with autoimmune diseases, including arthritis. Th17 cells contribute to the bone destruction in arthritis by upregulating RANKL on synovial fibroblasts as well as inducing local inflammation. Studies on the origin of Th17 in inflammation have shed light on the pathogenic conversion of Foxp3+ T cells...
July 19, 2018: Clinical and Experimental Immunology
Tomasz Janczi, Böhm B Beate, Yuliya Fehrl, Pangrazio DeGiacomo, Raimund W Kinne, Harald Burkhardt
OBJECTIVES: To investigate mechanisms underlying the capability of ADAM15 to transform FasL-mediated death inducing signals into pro-survival activation of Src and focal adhesion kinase (FAK) in rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Caspase-3/7 activity and apoptosis rate were determined in RASFs and ADAM15-transfected T/C28a4 cells upon Fas/CD95 triggering using enzyme assays and annexin-V staining. Phosphorylated Src and FAK was analyzed by immunoblotting...
July 13, 2018: Arthritis & Rheumatology
Jiajie Tu, Wenming Hong, Pengying Zhang, Xinming Wang, Heinrich Körner, Wei Wei
Fibroblast-like synoviocytes (FLS) and macrophage-like synoviocytes (MLS) are the two main cellular components of the synovium. It has been widely reported that FLS and MLS play essential roles in the joint pathology of rheumatoid arthritis (RA). Although various studies have analyzed both human and animal tissues and have shown that both cell types are involved in different stages of RA, ontology, and specific functions of both cell populations and their interactions are not well understood. In this review, we will summarize recent research on FLS and MLS in RA and focus on the development and function of two predominant synovial cell types...
2018: Frontiers in Immunology
Seungjin Choi, Kijun Lee, Hyerin Jung, Narae Park, Jaewoo Kang, Ki-Hoan Nam, Eun-Kyeong Kim, Ji Hyeon Ju, Kwi Young Kang
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes mild to severe joint inflammation. During RA pathogenesis, fibroblast-like synoviocytes (FLS) acquire a tumor-like phenotype and mediate cartilage destruction both directly and indirectly by producing proinflammatory cytokines and matrix metalloproteinases (MMPs). Kruppel-like factor (KLF) 4, a member of the KLF family, plays significant roles in cell survival, proliferation, and differentiation. A recent study reported increased expression of KLF4 in synovial tissue from RA patients...
2018: Frontiers in Immunology
Laura T Donlin, Deepak A Rao, Kevin Wei, Kamil Slowikowski, Mandy J McGeachy, Jason D Turner, Nida Meednu, Fumitaka Mizoguchi, Maria Gutierrez-Arcelus, David J Lieb, Joshua Keegan, Kaylin Muskat, Joshua Hillman, Cristina Rozo, Edd Ricker, Thomas M Eisenhaure, Shuqiang Li, Edward P Browne, Adam Chicoine, Danielle Sutherby, Akiko Noma, Chad Nusbaum, Stephen Kelly, Alessandra B Pernis, Lionel B Ivashkiv, Susan M Goodman, William H Robinson, Paul J Utz, James A Lederer, Ellen M Gravallese, Brendan F Boyce, Nir Hacohen, Costantino Pitzalis, Peter K Gregersen, Gary S Firestein, Soumya Raychaudhuri, Larry W Moreland, V Michael Holers, Vivian P Bykerk, Andrew Filer, David L Boyle, Michael B Brenner, Jennifer H Anolik
BACKGROUND: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples...
July 11, 2018: Arthritis Research & Therapy
Huan Liu, Shu-Ping Wei, Li-Qin Zhi, Li-Ping Liu, Tuan-Ping Cao, Su-Zhi Wang, Qing-Ping Chen, Dan Liu
Transcriptional regulation of the inducible nitric oxide synthase (iNOS) is critically involved in the pathogenesis and progression of rheumatoid arthritis (RA), but the specific transcription factors controlling this process remain largely unidentified. We discover here that the expression of the key erythroid factor globin transcription factor 1 (GATA1), was significantly higher in human RA synovial tissues than in osteoarthritis (OA) tissues. IL-6 induced the synovial GATA1 expression in a STAT3-dependent manner...
July 11, 2018: Microbiology and Immunology
Takahiro Yamashita, Hiroshi Hagino, Ikuta Hayashi, Masako Hayashibara, Atsushi Tanida, Keita Nagira, Ryohei Fukui, Hideki Nagashima
Objectives: Cathepsin K is expressed by osteoclasts and synovial fibroblasts and degrades key components of bone and cartilage. Inhibition of cathepsin K protease activity may be beneficial for the prevention of bone erosion and cartilage degradation in rheumatoid arthritis (RA). The collagen-induced arthritis (CIA) rat model is well established for studying the pathology and treatment of RA. We investigated the effect of ONO-KK1-300-01, a cathepsin K inhibitor (CKI), on arthritis and bone mineral density (BMD) in rats with CIA...
December 2018: Bone Reports
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