scholarly journals Molecular Mechanisms of Rheumatoid Arthritis Revealed by Categorizing Subtypes of Fibroblast-Like Synoviocytes

10.5772/29113 ◽  
2012 ◽  
Author(s):  
Katsuhiko Ishihara ◽  
Hideya Igarashi
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Fibroblast Like Synoviocytes

scholarly journals Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 795 ◽  
Author(s):  
Qing Zhang ◽  
Jia Liu ◽  
Mengmeng Zhang ◽  
Shujun Wei ◽  
Ruolan Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Herbal Medicines ◽  
Janus Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Signal Pathways ◽  
Apoptosis Induction ◽  
Apoptotic Pathway ◽  
Induction Of Apoptosis ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

scholarly journals Apoptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocytes: Possible Roles of Nitric Oxide and the Thioredoxin 1

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Huili Li ◽  
Ajun Wan
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Redox System ◽  
Chronic Inflammatory Disease ◽  
Thioredoxin 1 ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. The impaired apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is pivotal in this process. However, the molecular mechanisms responsible for the reduced apoptosis are not fully understood. Both nitric oxide and thioredoxin 1 as two important mediators are widely investigated in the pathogenesis of rheumatoid arthritis. Interestingly, studies have showed that thioredoxin 1 may serve as a master regulator of S-nitrosylation of caspase-3 to fine-tune apoptosisin vivo. Thus, it is anticipated that further investigations on the role of thioredoxin 1 in the S-nitrosylation and denitrosylation of caspase-3 in RA-FLS will likely provide a novel understanding of mechanisms implicated in the impaired apoptosis of RA-FLS. In this paper, we will provide an overview on pathways involved in the reduced apoptosis of RA-FLS and then discuss specially the possible roles of nitric oxide and the thioredoxin 1 redox system associated with apoptosis of RA-FLS.

scholarly journals Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes

2020 ◽  
Author(s):  
Zhaodong Li ◽  
Fangyuan Qi ◽  
Fan Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Western Blotting ◽  
Drug Targets ◽  
High Performance ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Bioinformatics Analysis ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Fibroblast Like Synoviocytes

Abstract Background: Rheumatoid arthritis- fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. Methods: The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. Results: In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose- and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3, THOC1, BUB1, and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles.Conclusions: WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA.

scholarly journals Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes

2020 ◽  
Author(s):  
Zhaodong Li ◽  
Fangyuan Qi ◽  
Fan Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Western Blotting ◽  
Drug Targets ◽  
High Performance ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Bioinformatics Analysis ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Fibroblast Like Synoviocytes

Abstract Background: Rheumatoid arthritis- fibroblast-like synoviocytes (RA-FLSs) play important roles in pathogenesis of rheumatoid arthritis (RA). Wantong Jingu Tablet (WJT), a mixture of traditional Chinese medicine, is a potentially effective therapy for RA, but its underlying mechanism is unclear. In this study, we explore the effects of WJT on human RA-FLSs and the underlying molecular mechanism. Methods: The major components of WJT were determined using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Cell proliferative ability was evaluated by CCK-8, colony formation assay, and EdU incorporation assay. Cell apoptotic capacity was examined by caspase-3 and caspase-9 activity test. Protein levels of Bax and Bcl-2 were investigated by western blotting. High-throughput sequencing and bioinformatics analysis were conducted to screen and identify targeted genes, followed by identification by qRT-PCR and western blotting. Results: In this study, we have identified 346 compounds in WJT. Our results showed that WJT inhibited the RA-FLSs proliferation, and promoted apoptosis in a dose- and time-dependent manner. More importantly, 184 differentially expressed genes (DEGs) has been screened after WJT treatment based on DEGSeq2 and 278 DEGs was identified by DEGSeq2 combined with WGCNA. Then, 10 hub genes were identified based on two different analyses, while the expression levels of only SMC3 , THOC1 , BUB1 , and STAG2 were decreased after WJT treatment, which was identical to the sequencing profiles.Conclusions: WJT exerted its anti-proliferation and pro-apoptosis effects possibly through suppressing the expression of SMC3, THOC1, BUB1, and STAG2 in RA-FLSs. Thus, therapeutics targeting these genes may be a promising strategy for rescuing RA. Keywords: Rheumatoid arthritis; bioinformatics; fibroblast-like synoviocytes; Wantong Jingu Tablet

scholarly journals Intervening the up-regulated SLC7A5 could mitigate the inflammatory mediator by mTOR-P70S6K signal in rheumatoid arthritis synoviocytes.

2020 ◽  
Author(s):  
Jing Xu ◽  
Congshan Jiang ◽  
Yongsong Cai ◽  
Yuanxu Guo ◽  
Xipeng Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Expression ◽  
Western Blotting ◽  
Molecular Mechanisms ◽  
Inflammatory Mediator ◽  
Protein Translation ◽  
Rheumatoid Arthritis Synoviocytes ◽  
Synovial Tissues ◽  
Signaling Activation ◽  
Fibroblast Like Synoviocytes

Abstract Objective The increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability are found in rheumatoid arthritis (RA). This study aimed to observe the effects of SLC7A5 (amino acid transporter) on synoviocytes of RA patients and pinpoint the underlying molecular mechanisms. Methods Synovial tissues were collected from OA and RA patients. Fibroblast-like synoviocytes (FLS) were isolated from synovial tissues from RA patients. SLC7A5 expression was evaluated by using RT-qPCR, immunofluorescence and Western blotting. Matrix metalloproteinases (MMPs) expression was evaluated by using RT-qPCR and Western blotting. RNAi and antibody blocking treatments were used to knockdown the expression of SLC7A5 or block its transporting function. Results The SLC7A5 expression was significantly upregulated in the FLS from RA patients compared with that in FLS from OA patients. Cytokine IL-1β played a crucial role in up-regulating SLC7A5 expression via NF-κB pathway in FLS. Intervening SLC7A5 expression with RNAi or blocking SLC7A5 function by monoclonal antibody could ameliorate the MMP3 and MMP13 protein expression. Furthermore, up regulation of SLC7A5 enhanced mTOR-P70SK6 signaling activation which could promote the protein translation of MMP3 and MMP13 in RA FLS. Conclusion SLC7A5 up-regulation could be induced by activated NF-κB pathway, further resulted in an enhanced mTOR-P70S6K activity and the protein expression of MMP3 and MMP13 in FLS from RA patients.

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

scholarly journals Molecular remission at T cell level in patients with rheumatoid arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun Inamo ◽  
Katsuya Suzuki ◽  
Masaru Takeshita ◽  
Yasushi Kondo ◽  
Yuumi Okuzono ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Disease Control ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Principal Component ◽  
Cell Level ◽  
Molecular Remission ◽  
Signature Genes

AbstractWhile numerous disease-modifying anti-rheumatic drugs (DMARDs) have brought about a dramatic paradigm shift in the management of rheumatoid arthritis (RA), unmet needs remain, such as the small proportion of patients who achieve drug-free status. The aim of this study was to explore key molecules for remission at the T cell level, which are known to be deeply involved in RA pathogenesis, and investigate the disease course of patients who achieved molecular remission (MR). We enrolled a total of 46 patients with RA and 10 healthy controls (HCs). We performed gene expression profiling and selected remission signature genes in CD4+ T cells and CD8+ T cells from patients with RA using machine learning methods. In addition, we investigated the benefits of achieving MR on disease control. We identified 9 and 23 genes that were associated with clinical remission in CD4+ and CD8+ T cells, respectively. Principal component analysis (PCA) demonstrated that their expression profiling was similar to those in HCs. For the remission signature genes in CD4+ T cells, the PCA result was reproduced using a validation cohort, indicating the robustness of these genes. A trend toward better disease control was observed during 12 months of follow-up in patients treated with tocilizumab in deep MR compared with those in non-deep MR, although the difference was not significant. The current study will promote our understanding of the molecular mechanisms necessary to achieve deep remission during the management of RA.

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