Faculty Opinions recommendation of Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis.

2008 ◽  
Author(s):  
Ladislav Senolt ◽  
Maria Filkova
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Altered Expression

scholarly journals Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis

2008 ◽  
Vol 58 (4) ◽  
pp. 1001-1009 ◽  
Author(s):  
Joanna Stanczyk ◽  
Deena M. Leslie Pedrioli ◽  
Fabia Brentano ◽  
Olga Sanchez-Pernaute ◽  
Christoph Kolling ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Altered Expression

scholarly journals Mechanism of miR-218-5p in autophagy, apoptosis and oxidative stress in rheumatoid arthritis synovial fibroblasts is mediated by KLF9 and JAK/STAT3 pathways

2021 ◽  
pp. jim-2020-001437
Author(s):  
Ming Chen ◽  
Minghui Li ◽  
Na Zhang ◽  
Wenwen Sun ◽  
Hui Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Signaling Pathway ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Reverse Transcription Pcr ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Interfering Rna ◽  
And Oxidative Stress

This study was aimed to investigate the effects of miR-218-5p on the proliferation, apoptosis, autophagy, and oxidative stress of rheumatoid arthritis synovial fibroblasts (RASFs), and the related mechanisms. Quantitative reverse transcription–PCR showed that the expression of miR-218-5p in rheumatoid arthritis synovial tissue was significantly higher than that in healthy synovial tissue. Compared with healthy synovial fibroblasts, miR-218-5p expression was obviously upregulated in RASFs, while KLF9 protein expression was markedly downregulated. Mechanistically, miR-218-5p could directly bind to the 3′ untranslated region of KLF9 to inhibit the expression of KLF9. Additionally, transfection of miR-218-5p small interfering RNA (siRNA) inhibited the proliferation but promoted apoptosis and autophagy of RASFs. Simultaneously, miR-218-5p silencing reduced reactive oxygen species and malondialdehyde levels and increased superoxide dismutase and glutathione peroxidase activity to improve oxidative stress in RASFs. More importantly, the introduction of KLF9 siRNA reversed the effects of miR-218-5p siRNA transfection on RASF proliferation, apoptosis, autophagy, and oxidative stress. What is more, silencing miR-218-5p inhibited the activation of JAK2/STAT3 signaling pathway by targeting KLF9. Collectively, knockdown of miR-218-5p could regulate the proliferation, apoptosis, autophagy and oxidative stress of RASFs by increasing the expression of KLF9 and inhibiting the activation of the JAK2/STAT3 signaling pathway, which may provide a potential target for the mechanism research of RA.

scholarly journals The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Li Zhu ◽  
Huaizhou Wang ◽  
Yu Wu ◽  
Zhengwen He ◽  
Yanghua Qin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Tissue ◽  
Active Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Serum Levels ◽  
Serum Markers ◽  
Effector Cells ◽  
Joint Replacement Surgery ◽  
Replacement Surgery ◽  
Synovial Tissues

Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n=20) were significantly higher than those in OA patients (n=16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.

scholarly journals FRI0005 DIVERSITY OF ANTI-CITRULLINATED PROTEIN ANTIBODY COMPOSITIONS INFLUENCE SYNOVIAL FIBROBLAST REACTIVITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 573.2-574
Author(s):  
M. Sun ◽  
B. Réthi ◽  
A. Krishnamurthy ◽  
V. Joshua ◽  
A. Circiumaru ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Monoclonal Antibodies ◽  
Synovial Tissue ◽  
Trichostatin A ◽  
Synovial Fibroblasts ◽  
Cross Reactivity ◽  
Anacardic Acid ◽  
Cellular Targets ◽  
Fibroblast Migration ◽  
Citrullinated Protein

Background:Anti-citrullinated protein antibodies (ACPAs) play an important role in rheumatoid arthritis (RA) pathogenesis. We hypothesized that the effect of these antibodies is mediated by their binding to synovial fibroblasts and inducing an increased mobility of fibroblasts1.Objectives:In our study, we analyzed and compared fibroblast modulation by ACPA pools obtained from different patients or by a set of monoclonal ACPAs with different fine specificity that were obtained from different tissue sites.Methods:Synovial fibroblasts were isolated from RA patients synovial tissue biopsies. Individual polyclonal ACPA and control IgGs were purified from sera of four ACPA-positive RA patients by affinity purification on protein G and CCP-2 columns. Monoclonal antibodies were derived from memory B cell isolated from blood2, synovial fluid or bronchoalveolar lavage of RA patients. Whole antibodies and F(ab’)2 fragments were tested in fibroblast migration using IncuCyte live-cell analysis. Blocking experiments were performed with soluble citrullinated proteins in SF migration. Cross-reactivity of the antibodies to citrullinated and acetylated epitopes was tested using PAD inhibitors (Cl-amidine and GSK199), histone acetyltransferases (anacardic acid) and deacetylases (trichostatin A). Binding patterns of monoclonal ACPAs, both whole and F(ab’)2 fragments were analyzed in synovial biopsies obtained from both healthy donors and RA patients.Results:Three out of four tested individual ACPA were able to promote fibroblast migration. Five out of nine tested monoclonal ACPAs stimulated fibroblast migration. One of these antibodies, clone 1325:01B09 is characterized by cross-reactivity to citrullinated, homocitrullinated and acetylated targets. The effect of 1325:01B09 on fibroblast migration was completely abolished by Cl-amidine or by pre-incubating the antibody with citrullinated fibrinogen or histone but not citrullinated enolase or vimentin. Despite the cross-reactivity to acetylated epitopes, neither anacardic acid nor trichostatin A could modulate the 1325:01B09 effect on fibroblast migration. F(ab’)2 fragments of this antibody stimulated fibroblast migration and labelled podoplanin-positive fibroblasts in inflamed RA synovium similarly to the intact antibody, indicating an Fc-independent effect.Conclusion:The effect on fibroblast mobility was likely to be mediated by binding to citrullinated epitopes but not through Fc receptors. Detection of fibroblast modulating ACPAs in majority of RA patients indicated that fibroblasts might be key cellular targets in disease pathogenesis, although individual variability might exist in the composition of ACPA cellular targets.References:[1]Sun M, Rethi B, Krishnamurthy A, et al. Anticitrullinated protein antibodies facilitate migration of synovial tissue-derived fibroblasts. Ann Rheum Dis 2019;78(12):1621-31. doi: 10.1136/annrheumdis-2018-214967 [published Online First: 2019/09/05][2]Amara K, Lena Israelsson, Ragnhild Stålesen, et al. A Refined Protocol for Identifying Citrulline-specific Monoclonal Antibodies from Single Human B Cells from Rheumatoid Arthritis Patient Material. Bio-protocol 2019;9(16)Disclosure of Interests:Meng Sun: None declared, Bence Réthi: None declared, Akilan Krishnamurthy: None declared, Vijay Joshua: None declared, Alexandra Circiumaru: None declared, Marianne Engström: None declared, Caroline Grönwall: None declared, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica, Khaled Amara: None declared, Lars Klareskog: None declared, Heidi Wähämaa: None declared, Anca Catrina: None declared

scholarly journals Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation

2011 ◽  
Vol 63 (2) ◽  
pp. 373-381 ◽  
Author(s):  
Joanna Stanczyk ◽  
Caroline Ospelt ◽  
Emmanuel Karouzakis ◽  
Andrew Filer ◽  
Karim Raza ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Altered Expression ◽  
Fibroblast Activation

scholarly journals POS0388 INTERLEUKIN 40 (IL-40) IS UP-REGULATED IN RHEUMATOID ARTHRITIS (RA) AND ASSOCIATED WITH DISEASE ACTIVITY, LEVELS OF AUTOANTIBODIES AND CHEMOKINES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 424.1-424
Author(s):  
A. Navrátilová ◽  
L. Andres Cerezo ◽  
H. Hulejova ◽  
V. Becvar ◽  
D. Tegzová ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Synovial Fluid ◽  
Disease Activity ◽  
B Cell ◽  
Synovial Tissue ◽  
Lupus Erythematosus ◽  
Synovial Fibroblasts ◽  
Clinical Activity

Background:Interleukin 40 (IL-40) is newly identified B cell - associated cytokine implicated in humoral immune responses and in B cell development. As B cells play a pivotal role in autoimmunity, we aimed to investigate the function of IL-40 in rheumatoid arthritis (RA).Objectives:The aim of our study was to determine the function of IL-40 in RA.Methods:IL-40 expression in the synovial tissue was determined by immunohistochemistry and immunofluorescence (n=4-5). IL-40 was analysed in the serum/synovial fluid of patients with RA (n=69), systemic lupus erythematosus (SLE; n=69), osteoarthritis (OA; n=44), and in healthy controls (HC; n=25). Given the association of IL-40 with B cells, we analysed the effect of rituximab therapy on the serum IL-40 in 19 patients with RA after 16 and 24 weeks of the therapy. The clinical activity of patients with RA was assessed according to the 28 joint count Disease Activity Score (DAS28). Levels of C-reactive protein (CRP) and autoantibodies were measured by routine laboratory techniques. In vitro experiments were performed in RA synovial fibroblasts (n=9). Levels of cytokines and inflammatory mediators were determined in serum, synovial fluid and supernatants using ELISA or multiplex immunoassay.Results:IL-40 was overexpressed in RA synovial tissue compared to OA, particularly by synovial fibroblasts and immune cells such as B and T lymphocytes, macrophages and neutrophils. The levels of IL-40 were significantly higher in the synovial fluid of RA patients compared to OA (33.2 (6.6-68.9) vs. 0.7 (0.1-2.4) ng/ml; p<0.0001). In addition, IL-40 was increased in the serum of RA patients compared to SLE, OA or HC (4.8 (1.7-24.9) vs. 1.4 (1.0-1.9), 1.6 (0.6-3.1) or 1.5 (0.7-2.7) ng/ml; p<0.0001 for all) and decreased after 16 (p<0.01) and 24 weeks (p<0.001) in a subgroup of rituximab treated patients with RA. IL-40 levels in RA patients correlated with autoantibodies rheumatoid factor (IgM) and anti-citrullinated protein antibody (ACPA) in the serum (p<0.0001 and p<0.01) as well as in the synovial fluid (p<0.0001 and p<0.001). IL-40 in RA synovial fluid was also significantly associated with DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), number of swollen joints (p<0.05) and neutrophil attractants IL-8 (p<0.01) and MIP-1α (p<0.01). RA synovial fibroblasts exposed to recombinant IL-40 increased secretion of IL-8 (p<0.01), MCP-1 (p<0.05) and MMP-13 (p<0.01) compared to unstimulated cells in in vitro conditions.Conclusion:Our results show for the first time that IL-40 is elevated in RA and decreases following B-cell depletion therapy. The association of IL-40 with autoantibodies and chemokines may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 by synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.Acknowledgements:Supported by MHCR 023728 a SVV 260 523Disclosure of Interests:None declared

scholarly journals A thyroid hormone network exists in synovial fibroblasts of rheumatoid arthritis and osteoarthritis patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna-Sophia Pörings ◽  
Torsten Lowin ◽  
Bianca Dufner ◽  
Joachim Grifka ◽  
Rainer H. Straub
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Thyroid Hormone ◽  
Synovial Fluid ◽  
Thyroid Hormones ◽  
Synovial Tissue ◽  
Hormone Receptors ◽  
Synovial Fibroblasts ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Abstract While patients with rheumatoid arthritis (RA) sometimes demonstrate thyroidal illness, the role of thyroid hormones in inflamed synovial tissue is unknown. This is relevant because thyroid hormones stimulate immunity, and local cells can regulate thyroid hormone levels by deiodinases (DIO). The study followed the hypothesis that elements of a thyroid hormone network exist in synovial tissue. In 12 patients with RA and 32 with osteoarthritis (OA), we used serum, synovial fluid, synovial tissue, and synovial fibroblasts (SF) in order to characterize the local thyroid hormone network using ELISAs, immunohistochemistry, imaging methods, tissue superfusion studies, cell-based ELISAs, flow cytometry, and whole genome expression profiling. Serum/synovial fluid thyroid hormone levels were similar in RA and OA (inclusion criteria: no thyroidal illness). The degradation product termed reverse triiodothyronine (reverse T3) was much lower in serum compared to synovial fluid indicating biodegradation of thyroid hormones in the synovial environment. Superfusion experiments with synovial tissue also demonstrated biodegradation, particularly in RA. Cellular membrane transporters of thyroid hormones, DIOs, and thyroid hormone receptors were present in tissue and SF. Density of cells positive for degrading DIOs were higher in RA than OA. TNF increased protein expression of degrading DIOs in RASF and OASF. Gene expression studies of RASF revealed insignificant gene regulation by bioactive T3. RA and OA synovial tissue/SF show a local thyroid hormone network. Thyroid hormones undergo strong biodegradation in synovium. While bioactive T3 does not influence SF gene expression, SF seem to have a relay function for thyroid hormones.

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