scholarly journals Potential mechanisms of action of celastrol against rheumatoid arthritis: transcriptomic and proteomic analysis

2020 ◽  
Author(s):  
Xinqiang Song ◽  
SONG Xinqiang ◽  
DAI Erqin ◽  
ZHANG Yu ◽  
DU Hongtao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Quantitative Proteomics ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Label Free ◽  
Expression Of Genes ◽  
Differential Expression Of Genes ◽  
Fibroblast Like Synoviocytes

Abstract Background: The natural triterpene celastrol exhibits potential anti-inflammatory activity in inflammatory diseases such as rheumatoid arthritis (RA). Methods: Here we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking. Results: Expression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix. Conclusions: These results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

scholarly journals Potential mechanisms of action of celastrol against rheumatoid arthritis: transcriptomic and proteomic analysis

2020 ◽  
Author(s):  
Xinqiang Song ◽  
Erqin Dai ◽  
Yu Zhang ◽  
Hongtao Du ◽  
Lei Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Quantitative Proteomics ◽  
Inflammatory Diseases ◽  
Mechanisms Of Action ◽  
Label Free ◽  
Expression Of Genes ◽  
Differential Expression Of Genes ◽  
Fibroblast Like Synoviocytes

AbstractBackgroundThe natural triterpene celastrol exhibits potential anti-inflammatory activity in inflammatory diseases such as rheumatoid arthritis (RA).MethodsHere we explored through what proteins and processes celastrol may act in activated fibroblast-like synoviocytes (FLS) from RA patients. Differential expression of genes and proteins after celastrol treatment of FLS was examined using RNA sequencing, label-free relatively quantitative proteomics and molecular docking.ResultsExpression of 26,565 genes and 3,372 proteins was analyzed. Celastrol was associated with significant changes in genes that respond to oxidative stress and oxygen levels, as well as genes that stabilize or synthesize components of the extracellular matrix.ConclusionsThese results identify several potential mechanisms through which celastrol may inhibit inflammation in RA.

Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases

2000 ◽  
Vol 21 (2) ◽  
pp. 78-82 ◽  
Author(s):  
Paul P. Tak ◽  
Nathan J. Zvaifler ◽  
Douglas R. Green ◽  
Gary S. Firestein
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Inflammatory Diseases

scholarly journals Comprehensive Profiling of Cartilage Extracellular Matrix Formation and Maturation Using Sequential Extraction and Label-free Quantitative Proteomics

2010 ◽  
Vol 9 (6) ◽  
pp. 1296-1313 ◽  
Author(s):  
Richard Wilson ◽  
Anders F. Diseberg ◽  
Lavinia Gordon ◽  
Snezana Zivkovic ◽  
Liliana Tatarczuch ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Sequential Extraction ◽  
Quantitative Proteomics ◽  
Label Free ◽  
Cartilage Extracellular Matrix

scholarly journals Oxidative Stress in Rheumatoid Arthritis: What the Future Might Hold regarding Novel Biomarkers and Add-On Therapies

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Lucas José Sá da Fonseca ◽  
Valéria Nunes-Souza ◽  
Marília Oliveira Fonseca Goulart ◽  
Luiza Antas Rabelo
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Chronic Arthritis ◽  
Therapeutic Interventions ◽  
Antioxidant Defenses ◽  
Oxidative Stress Biomarkers ◽  
Early Stages ◽  
Articular Damage

Numerous rheumatologic autoimmune diseases, among which rheumatoid arthritis, are chronic inflammatory diseases capable of inducing multiple cumulative articular and extra-articular damage, if not properly treated. Nevertheless, benign conditions may, similarly, exhibit arthritis as their major clinical finding, but with short-term duration instead, and evolve to spontaneous resolution in a few days to weeks, without permanent articular damage. Such distinction—self-limited arthritis with no need of immunosuppressive treatment or chronic arthritis at early stages?—represents one of the greatest challenges in clinical practice, once many metabolic, endocrine, neoplastic, granulomatous, infectious diseases and other autoimmune conditions may mimic rheumatoid arthritis. Indeed, the diagnosis of rheumatoid arthritis at early stages is a crucial step to a more effective mitigation of the disease-related damage. As a prototype of chronic inflammatory autoimmune disease, rheumatoid arthritis has been linked to oxidative stress, a condition in which the pool of reactive oxygen species increases over time, either by their augmented production, the reduction in antioxidant defenses, or the combination of both, ultimately implying compromise in the redox signaling. The exact mechanisms through which oxidative stress may contribute to the initiation and perpetuation of local (in the articular milieu) and systemic inflammation in rheumatoid arthritis, particularly at early stages, still remain to be determined. Furthermore, the role of antioxidants as therapeutic adjuvants in the control of disease activity seems to be overlooked, as a little number of short studies addressing this issue is currently found. Thus, the present review focuses on the binomial rheumatoid arthritis-oxidative stress, bringing insights into their pathophysiological relationships, as well as the implications of potential diagnostic oxidative stress biomarkers and therapeutic interventions directed to the oxidative status in patients with rheumatoid arthritis.

scholarly journals A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying-Jie Chen ◽  
Yu-Xi Liu ◽  
Jia-Ying Wu ◽  
Chun-Yu Li ◽  
Min-Min Tang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Ethanolic Extract ◽  
Collagen Induced Arthritis ◽  
Protein Levels ◽  
Stat3 Signaling ◽  
Traditional Remedy ◽  
Synovial Tissues ◽  
Underlying Mechanisms ◽  
Fibroblast Like Synoviocytes

AbstractFibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.

scholarly journals KDM4B Overexpression Promotes the Growth, Migration, and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Activating STAT3 Pathway

2021 ◽  
Author(s):  
Xin Zhang ◽  
He Nan ◽  
Jialong Guo ◽  
Jinyu Liu
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Western Blot ◽  
Inflammatory Diseases ◽  
Migration And Invasion ◽  
Control Group ◽  
Inflammatory Microenvironment ◽  
Stat3 Signaling ◽  
Fibroblast Like Synoviocytes ◽  
Invasion Assays

AbstractIn rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) present a unique aggressive phenotype and have a passive response to the inflammatory microenvironment, which are critical for the disease’s progression. KDM4B, as a histone demethylase, functions as an oncogenic factor in many cancers and is implicated in osteoclastogenesis as well as pro-inflammatory cytokine release in inflammatory diseases. However, the effects of KDM4B on RA FLS have not been reported. To investigate this issue, our study determined the expression of KDM4B in RA FLS using RT-qPCR and western blot. The effects of KDM4B on RA FLS viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, transwell migration, and invasion assays. Furthermore, the interaction of KDM4B with STAT3 signaling was studied by western blot, MTT, flow cytometry, transwell migration, and invasion assays. The experimental results showed that KDM4B expression was upregulated in RA synovial tissues and FLS as compared to healthy control tissues and normal FLS. Knockdown of KDM4B obviously suppressed RA FLS viability, migration and invasion, and induced apoptosis. In addition, knockdown of KDM4B in RA FLS decreased the expression of p-STAT3 and MMP-9 but increased cleaved caspase-3 expression compared with the control group. Moreover, KDM4B overexpression could promote cell growth, migration and invasion, and suppress apoptosis in RA FLS by activating STAT3 signaling. Therefore, these findings provide new insight for understanding the pathogenesis of RA and indicate that KDM4B may have a potential to be an effective therapeutic target for RA.

scholarly journals Cumulative effect of systemic inflammation and oxidative stress in 40 known cases of active rheumatoid arthritis

2015 ◽  
Vol 1 (1) ◽  
pp. 7 ◽  
Author(s):  
Rahul Saxena ◽  
Shilpa Suneja ◽  
Raj Saxena ◽  
Dilutpal Sharma ◽  
Alok Milton Lal
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Systemic Inflammation ◽  
Inflammatory Diseases ◽  
Cumulative Effect ◽  
Extensive Literature ◽  
Reactive Protein ◽  
Ceruloplasmin Level ◽  
Student’S T

<p class="abstract"><strong>Background:</strong> Oxidative stress has been implicated in the pathophysiology of a number of diseases such as cancer, hypertension and inflammatory diseases. Although previous evidences provided extensive literature about the biological role of antioxidant enzymes in rheumatoid arthritis (RA), there is a paucity of satisfactory explanation regarding the alteration in the level of antioxidant enzymes along with marker of systemic inflammation in RA. The objective of present study was to estimate the level of C-reactive protein (CRP), Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GSHPx) and Ceruloplasmin in active RA patients.</p><p class="abstract"><strong>Methods:</strong> 40 patients of either sex (30-50 years age group) suffering from active RA and 40 normal healthy individuals served as control; were included in the study. Above mentioned parameters were estimated using standard methods and data from patients and controls were compared by using Student’s t-test.<strong></strong></p><p class="abstract"><strong>Results:</strong> Erythrocyte SOD, CAT and GSHPx activity were significantly low in RA subjects (P&lt;0.001) whereas plasma Ceruloplasmin level was found to be significantly high (P&lt;0.001) as compared to healthy controls.</p><p><strong>Conclusions:</strong> These findings suggest that combined effect of inflammation and free radical generation is involved in the pathogenesis of active RA, characterized by imbalance in antioxidant enzyme status and enhanced CRP levels, which served as an excellent marker of oxidative stress and systemic inflammation in active RA.</p>

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