scholarly journals Inhibition of BMP3 increases the inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis

Aging ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 12305-12323
Author(s):  
Biao Song ◽  
Xiaofeng Li ◽  
Qingqing Xu ◽  
Suqin Yin ◽  
Sha Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Fibroblast Like Synoviocytes

scholarly journals Lnc RNA ZFAS1 regulates the proliferation, apoptosis, inflammatory response and autophagy of fibroblast-like synoviocytes via miR-2682-5p/ADAMTS9 axis in rheumatoid arthritis

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Shanshan Yang ◽  
Wei Yin ◽  
Yan Ding ◽  
Fan Liu
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Inflammatory Response ◽  
Large Subunit ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Behaviors ◽  
Synovial Tissues ◽  
Related Proteins ◽  
Fibroblast Like Synoviocytes

Abstract Backgrounds: Rheumatoid arthritis (RA) is a frequent autoimmune disease. Emerging evidence indicated that ZNFX1 antisense RNA1 (ZFAS1) participates in the physiological and pathological processes in RA. However, knowledge of ZFAS1 in RA is limited, the potential work pathway of ZFAS1 needs to be further investigated. Methods: Levels of ZFAS1, microRNA (miR)-2682-5p, and ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9) were estimated using quantitative real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to explore the ability of cell proliferation in fibroblast-like synoviocytes (FLS-RA). Cell apoptosis was measured via flow cytometry. Also, levels of ADAMTS9, apoptosis-related proteins, cleaved-caspase-3 (active large subunit), and autophagy-related proteins were identified adopting Western blot. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the productions of inflammatory cytokines. Beside, the interrelation between miR-2682-5p and ZFAS1 or ADAMTS9 was verified utilizing dual-luciferase reporter assay. Results: High levels of ZFAS1 and ADAMTS9, and a low level of miR-2682-5p were observed in RA synovial tissues and FLS-RA. Knockdown of ZFAS1 led to the curbs of cell proliferation, inflammation, autophagy, and boost apoptosis in FLS-RA, while these effects were abolished via regaining miR-2682-5p inhibition. Additionally, the influence of miR-2682-5p on cell phenotypes and inflammatory response were eliminated by ADAMTS9 up-regulation in FLS-RA. Mechanically, ZFAS1 exerted its role through miR-2682-5p/ADAMTS9 axis in RA. Conclusion: ZFAS1/miR-2682-5p/ADAMTS9 axis could modulate the cell behaviors, inflammatory response in FLS-RA, might provide a potential therapeutic target for RA treatment.

scholarly journals Reduction of Oxidative Stress in Peripheral Blood Mononuclear Cells Attenuates the Inflammatory Response of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

2021 ◽  
Vol 22 (22) ◽  
pp. 12411
Author(s):  
Ha-Reum Lee ◽  
Su-Jin Yoo ◽  
Jinhyun Kim ◽  
Chan Keol Park ◽  
Seong Wook Kang
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cell ◽  
Inflammatory Response ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
T Cell Subsets ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Fibroblast Like Synoviocytes

The production and oxidation mechanism of reactive oxygen species (ROS) are out of balance in rheumatoid arthritis (RA). However, the correlation between ROS and T cell subsets in RA remains unclear. Peripheral blood mononuclear cells (PBMCs) from patients with RA (n = 40) and healthy controls (n = 10) were isolated from whole blood samples. Synovial tissues (n = 3) and synovial fluid (n = 10) were obtained from patients with RA. The repartition of T cell subsets and expression of ROS and cytokines were examined according to RA severity. Fibroblast-like synoviocytes (FLSs) from patients with RA were stimulated with PBMCs and the expression of inflammation-related molecules were measured by RT-PCR and cytokine array. Regulatory T cells from patients with moderate (5.1 > DAS28 ≥ 3.2) RA showed the highest expression of mitochondrial ROS among the groups based on disease severity. Although ROS levels steadily increased with RA severity, there was a slight decline in severe RA (DAS28 ≥ 5.1) compared with moderate RA. The expression of inflammatory cytokines in RA FLSs were significantly inhibited when FLSs were co-cultured with PBMCs treated with ROS inhibitor. These findings provide a novel approach to suppress inflammatory response of FLSs through ROS regulation in PBMCs.

scholarly journals YAP/TAZ: Key Players for Rheumatoid Arthritis Severity by Driving Fibroblast Like Synoviocytes Phenotype and Fibro-Inflammatory Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Robin Caire ◽  
Estelle Audoux ◽  
Guillaume Courbon ◽  
Eva Michaud ◽  
Claudie Petit ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Transcriptional Activity ◽  
Bone Erosion ◽  
Fold Increase ◽  
Cell Phenotype ◽  
Apoptosis Resistance ◽  
Arthritis Severity ◽  
Fibroblast Like Synoviocytes

ObjectiveThe role of YAP/TAZ, two transcriptional co-activators involved in several cancers, was investigated in rheumatoid arthritis (RA).MethodsFibroblast like synoviocytes (FLS) from patients with RA or osteoarthritis were cultured in 2D or into 3D synovial organoids. Arthritis rat model (n=28) and colitis mouse model (n=21) were used. YAP/TAZ transcriptional activity was inhibited by verteporfin (VP). Multiple techniques were used to assess gene and/or protein expression and/or localization, cell phenotype (invasion, proliferation, apoptosis), bone erosion, and synovial stiffness.ResultsYAP/TAZ were transcriptionally active in arthritis (19-fold increase for CTGF expression, a YAP target gene, in RA vs. OA organoids; p<0.05). Stiff support of culture or pro-inflammatory cytokines further enhanced YAP/TAZ transcriptional activity in RA FLS. Inhibiting YAP/TAZ transcriptional activity with VP restored a common phenotype in RA FLS with a decrease in apoptosis resistance, proliferation, invasion, and inflammatory response. Consequently, VP blunted hyperplasic lining layer formation in RA synovial organoids. In vivo, VP treatment strongly reduced arthritis severity (mean arthritic index at 3.1 in arthritic group vs. 2.0 in VP treated group; p<0.01) by restoring synovial homeostasis and decreasing systemic inflammation. YAP/TAZ transcriptional activity also enhanced synovial membrane stiffening in vivo, thus creating a vicious loop with the maintenance of YAP/TAZ activation over time in FLS. YAP/TAZ inhibition was also effective in another inflammatory model of mouse colitis.ConclusionOur work reveals that YAP/TAZ were critical factors during arthritis. Thus, their transcriptional inhibition could be relevant to treat inflammatory related diseases.

Effect of CD95 on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes

2014 ◽  
Vol 290 (2) ◽  
pp. 209-216 ◽  
Author(s):  
Xiaoqiong Li ◽  
Zhanfeng Zhang ◽  
Anping Peng ◽  
Min He ◽  
Jianhua Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Fibroblast Like Synoviocytes

scholarly journals Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes via the MAPK p38/PPARγ/CTGF Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ying Han ◽  
Jing Wang ◽  
Meng Jin ◽  
Lin Jia ◽  
Cuihuan Yan ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Cyclin D1 ◽  
Caspase 3 ◽  
S Phase ◽  
Cell Counting ◽  
G1 Phase ◽  
Migration And Invasion ◽  
Pparγ Agonist ◽  
Fibroblast Like Synoviocytes

Introduction. The current study is aimed at exploring the effect of Shentong Zhuyu Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and its underlying molecular mechanism. Materials and Methods. The type II collagen-induced arthritis (CIA) model was established. Subsequently, the RA-FLS were isolated from the CIA rat model and identified by immunohistochemistry. The viability, apoptosis, cell cycle, migration, and invasion of RA-FLS were detected by the cell counting kit 8 (CCK-8) assay, flow cytometry, wound-healing assay, and transwell invasion assay, respectively. The levels of MAPK p38, PPARγ, CTGF, Bcl-2, Bax, caspase-3, IL-1β, MMP-3, CDK4, and cyclin D1 were determined by qRT-PCR and western blotting, respectively. Results. After treatment with Shentong Zhuyu Decoction medicated serum, the OD570 value, migrative and invasive abilities, and the secretion of IL-1β, MMP-3 were remarkably decreased in RA-FLS, while the apoptosis rate was increased. Further, results showed that Shentong Zhuyu Decoction inhibited the transition from the G1 phase to S phase. Additionally, Shentong Zhuyu Decoction significantly inhibited the expression of Bcl-2, CDK4, cyclin D1, MAPK p-p38, and CTGF, whereas elevated the levels of Bax, caspase-3, and PPARγ. Importantly, the effects of Shentong Zhuyu Decoction were consistent with the trends of MAPK P38 inhibitor (SB203580) and PPARγ agonist (GW1929). Conclusions. Shentong Zhuyu Decoction inhibited viability, inflammatory response, migration, invasion, and transition from the G1 phase to S phase and promoted apoptosis of RA-FLS via the MAPK p38/PPARγ/CTGF pathway.

scholarly journals Antagonism of NK-1R using aprepitant suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes

2019 ◽  
Vol 47 (1) ◽  
pp. 1628-1634 ◽  
Author(s):  
Xiaoping Liu ◽  
Yuelan Zhu ◽  
Wei Zheng ◽  
Tangliang Qian ◽  
Haiyu Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Fibroblast Like Synoviocytes
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