OP0133 DNA Demethylation Pathway Analysis in Rheumatoid Arthritis Synovial Fibroblasts and Macrophages

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 106.2-107
Author(s):  
E. Karouzakis ◽  
F. Sun ◽  
R.E. Gay ◽  
B.A. Michel ◽  
S. Ye ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Pathway Analysis ◽  
Synovial Fibroblasts ◽  
Dna Demethylation ◽  
Demethylation Pathway

scholarly journals Proteasome inhibition restored the reduced expression of fibroblast growth factor receptor 3 in rheumatoid arthritis synovial fibroblasts

2020 ◽  
Author(s):  
Michel Neidhart ◽  
Emmanuel Karouzakis ◽  
Sandro Fucentese ◽  
Oliver Distler ◽  
Astrid Jüngel
Keyword(s):  
Rheumatoid Arthritis ◽  
Proteasome Inhibitors ◽  
Growth Factor Receptor ◽  
Synovial Fibroblasts ◽  
Dna Demethylation ◽  
Proteasome Activity ◽  
Signal Pathways ◽  
20S Proteasome ◽  
Fibroblast Growth ◽  
Synovial Hyperplasia

Abstract Background. Synovial hyperplasia is a hallmark of rheumatoid arthritis (RA). This might be associated with an imbalance of growth-promoting and apoptotic pathways, among them fibroblast growth factors (FGFs) and their receptors (FGFRs) . The aim was to investigate differences in FGFRs and to explore the factors that might explain the differences between RA and osteoarthritis (OA) synovial fibroblasts. Methods. To assess FGFRs expression, immunohistochemistry, flow cytometry and RT-qPCR were performed. The cells were treated with TNFa, FGF2, a demethylation agent, PKA-mimics or inhibitors, hypoxia-mimics or proteasome inhibitors. Proliferation was measured using the CCK8 assay and 20S proteasome activity by a fluorescent assay. Results. In RA, FGFR3 protein was decreased in the synovial lining layer (p<0.005) and in cultured RA synovial fibroblasts (RASF) (n=10, p < 0.01). Transcription was unchanged and DNA demethylation decrease its expression. Exposure to TNFa or FGF2 had no effect on FGFR3. PKA-modulation and hypoxia-mimics induced transient changes only. Most interesting, in RASF, the proteasome inhibitor MG-132 restored FGFR3 expression (p<0.001) to levels measured in normal or OA synovial fibroblasts. MG-132 abolished the enhanced proliferative response of RASF to FGF2 (p<0.005). Increased 20S proteasome activity correlated (r=- 0.63, p<0.05) with decreased expression of FGFR3. Conclusions. The expression of FGFR3 is reduced in RA partially due to an increased degradation in proteasomes. This leads to an imbalance in the FGF-related signal pathways and may contribute to synovial hyperplasia. Proteasome inhibitors could represent a novel therapeutic strategy in RA, particularly to prevent synovial hyperplasia.

The Role of Synovial Fibroblasts in Mediating Joint Destruction in Rheumatoid Arthritis

2005 ◽  
Vol 11 (5) ◽  
pp. 563-568 ◽  
Author(s):  
Ingmar Meinecke ◽  
Edita Rutkauskaite ◽  
Steffen Gay ◽  
Thomas Pap
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Synovial Fibroblasts

FRI0020 BMP-2 and TGF-B Inhibit IL-34 Expression in Rheumatoid Arthritis Synovial Fibroblasts

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 432.3-433
Author(s):  
M. Chemel-Mary ◽  
B. Legoff ◽  
Y. Maugars ◽  
D. Heymann ◽  
F. Verrechia
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts

Notch‐1 and Notch‐3 Mediates Hypoxia‐Induced Synovial Fibroblasts Activation in Rheumatoid Arthritis

2021 ◽  
Author(s):  
Jianhai Chen ◽  
Wenxiang Cheng ◽  
Jian Li ◽  
Yan Wang ◽  
Jingqin Chen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Notch 1 ◽  
Notch 3

scholarly journals MiR-140-3p inhibits the cell viability and promotes apoptosis of synovial fibroblasts in rheumatoid arthritis through targeting sirtuin 3

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Beibei Zu ◽  
Lin Liu ◽  
Jingya Wang ◽  
Meirong Li ◽  
Junxia Yang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Pearson Correlation ◽  
Fibrous Tissue ◽  
Synovial Fibroblasts ◽  
Cell Counting ◽  
Sirtuin 3 ◽  
Fibrous Tissues

Abstract Background Synovial fibroblasts (SFs) with the abnormal expressions of miRNAs are the key regulator in rheumatoid arthritis (RA). Low-expressed miR-140-3p was found in RA tissues. Therefore, we attempted to investigate the effect of miR-140-3p on SFs of RA. Methods RA and normal synovial fibrous tissue were gathered. The targets of miR-140-3p were found by bioinformatics and luciferase analysis. Correlation between the expressions of miR-140-3p with sirtuin 3 (SIRT3) was analyzed by Pearson correlation analysis. After transfection, cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-140-3p, SIRT3, Ki67, Bcl-2, Bax, and cleaved Caspase-3 were detected by RT-qPCR or western blot. Results Low expression of miR-140-3p and high expression of SIRT3 were found in RA synovial fibrous tissues. SIRT3 was a target of miR-140-3p. SIRT3 expression was negatively correlated to the expression of miR-140-3p. MiR-140-3p mimic inhibited the MH7A cell viability and the expressions of SIRT3, Ki67, and Bcl-2 and promoted the cell apoptosis and the expressions of Bax and cleaved Caspase-3; miR-140-3p inhibitor showed an opposite effect to miR-140-3p mimic on MH7A cells. SIRT3 overexpression not only promoted the cell viability and inhibited cell apoptosis of MH7A cells but also reversed the effect of miR-140-3p mimic had on MH7A cells. Conclusions The results in this study revealed that miR-140-3p could inhibit cell viability and promote apoptosis of SFs in RA through targeting SIRT3.

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 OP0022 Molecular profile of rheumatoid arthritis-synovial fibroblasts during proliferation

2001 ◽  
Author(s):  
K Masuda ◽  
R Masuda ◽  
M Neidhart ◽  
CA Seemayer ◽  
BR Simmen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fibroblasts ◽  
Molecular Profile
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