Therapeutic Potential of Exosomal circRNA Derived from Synovial Mesenchymal Cells via Targeting circEDIL3/miR-485-3p/PIAS3/STAT3/VEGF Functional Module in Rheumatoid Arthritis

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the bone and cartilage. In RA pathogenesis, various molecules in effector cells (i.e., immune cells and mesenchymal cells) are dysregulated by genetic and environmental factors. Synovial fibroblasts (SFs), the most abundant resident mesenchymal cells in the synovium, are the major local effectors of the destructive joint inflammation and exert their effects through the pathogenic production of molecules such as interleukin-6. Main body To date, more than 100 RA susceptibility loci have been identified in genome-wide association studies (GWASs), and finding novel therapeutic targets utilizing genome analysis is considered a promising approach because some candidate causal genes identified by GWASs have previously been established as therapeutic targets. For further exploration of RA-responsible cells and cell type-specific therapeutic targets, integrated analysis (or functional genome analysis) of the genome and intermediate traits (e.g., transcriptome and epigenome) is crucial. Conclusion This review builds on the existing knowledge regarding the epigenomic abnormalities in RASFs and discusses the recent advances in single-cell analysis, highlighting the prospects of SFs as targets for safer and more effective therapies against RA.

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The therapeutic potential of plant flavonoids on rheumatoid arthritis

Critical Reviews in Food Science and Nutrition ◽

10.1080/10408398.2016.1246413 ◽

2017 ◽

Vol 57 (17) ◽

pp. 3601-3613 ◽

Cited By ~ 15

Author(s):

Samuel D. Hughes ◽

Natkunam Ketheesan ◽

Nagaraja Haleagrahara

Keyword(s):

Rheumatoid Arthritis ◽

Therapeutic Potential

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Quercetin: A Potential Candidate For The Treatment Of Arthritis

Current Molecular Medicine ◽

10.2174/1566524021666210315125330 ◽

2021 ◽

Vol 21 ◽

Author(s):

Ahsas Goyal ◽

Neetu Agrawal

Keyword(s):

Rheumatoid Arthritis ◽

Medicinal Plants ◽

Therapeutic Potential ◽

Gouty Arthritis ◽

Potential Candidate ◽

Protective Effects ◽

Preclinical Models ◽

Healthy Life ◽

Health Promoting ◽

Dietary Component

: Diet plays a significant role in ensuring healthy life and the bioactive compounds present in food and medicinal plants may be developed as drugs that combat various illnesses. A bioactive flavanoid, quercetin which is a dietary component possesses numerous health-promoting effects. In preclinical models of rheumatoid arthritis, gouty arthritis and osteoarthritis, quercetin has shown significant joint protective effects. Taking into account the significance of this compound, the present review discusses its anti-arthritic properties, demonstrating its mechanism of action for the treatment of arthritis with its therapeutic potential.

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Anti-proliferative and anti-inflammatory activities of belinostat: Therapeutic potential for rheumatoid arthritis?

Bone ◽

10.1016/j.bone.2008.07.199 ◽

2008 ◽

Vol 43 ◽

pp. S99

Author(s):

Haishu Lin ◽

Qiuyi Choo ◽

Jia Yang ◽

Yoshiya Tanaka ◽

Sui Yung Chan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Therapeutic Potential ◽

Anti Inflammatory

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Liposome/gold hybrid nanoparticle encoded with CoQ10 (LGNP-CoQ10) suppressed rheumatoid arthritis via STAT3/Th17 targeting

PLoS ONE ◽

10.1371/journal.pone.0241080 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241080

Author(s):

Jooyeon Jhun ◽

Jeonghyeon Moon ◽

Jaeyoon Ryu ◽

Yonghee Shin ◽

Seangyoun Lee ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mononuclear Cells ◽

Therapeutic Potential ◽

Human Peripheral Blood ◽

Treated Group ◽

Hybrid Nanoparticles ◽

Peripheral Blood Mononuclear ◽

Hematoxylin And Eosin ◽

Anti Inflammatory ◽

Safranin O

Coenzyme Q10 (CoQ10), also known as ubiquinone, is a fat-soluble antioxidant. Although CoQ10 has not been approved as medication by the Food and Drug Administration, it is widely used in dietary supplements. Some studies have shown that CoQ10 has anti-inflammatory effects on various autoimmune disorders. In this study, we investigated the anti-inflammatory effects of liposome/gold hybrid nanoparticles encoded with CoQ10 (LGNP-CoQ10). Both CoQ10 and LGNP-CoQ10 were administered orally to mice with collagen-induced arthritis (CIA) for 10 weeks. The inflammation pathology of joint tissues of CIA mice was then analyzed using hematoxylin and eosin and Safranin O staining, as well as immunohistochemistry analysis. We obtained immunofluorescence staining images of spleen tissues using confocal microscopy. We found that pro-inflammatory cytokines were significantly decreased in LGNP-CoQ10 injected mice. Th17 cell and phosphorylated STAT3-expressed cell populations were also decreased in LGNP-CoQ10 injected mice. When human peripheral blood mononuclear cells (PBMCs) were treated with CoQ10 and LGNP-CoQ10, the IL-17 expression of PBMCs in the LGNP-CoQ10-treated group was significantly reduced. Together, these results suggest that LGNP-CoQ10 has therapeutic potential for the treatment of rheumatoid arthritis.

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Therapeutic Potential of a Novel Bifidobacterium Identified Through Microbiome Profiling of RA Patients With Different RF Levels

Frontiers in Immunology ◽

10.3389/fimmu.2021.736196 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yunju Jeong ◽

JooYeon Jhun ◽

Seon-Yeong Lee ◽

Hyun Sik Na ◽

JeongWon Choi ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Relative Abundance ◽

Th17 Cells ◽

Mononuclear Cells ◽

Therapeutic Potential ◽

Human Peripheral Blood ◽

Cartilage Damage ◽

Therapeutic Effects ◽

Bioinformatics Analyses ◽

Proinflammatory Mediators

The potential therapeutic effects of probiotic bacteria in rheumatoid arthritis (RA) remain controversial. Thus, this study aimed to discover potential therapeutic bacteria based on the relationship between the gut microbiome and rheumatoid factor (RF) in RA. Bacterial genomic DNA was extracted from the fecal samples of 93 RA patients and 16 healthy subjects. Microbiota profiling was conducted through 16S rRNA sequencing and bioinformatics analyses. The effects of Bifidobacterium strains on human peripheral blood mononuclear cells and collagen-induced arthritis (CIA) mice were assessed. Significant differences in gut microbiota composition were observed in patients with different RF levels. The relative abundance of Bifidobacterium and Collinsella was lower in RF-high than in RF-low and RF-negative RA patients, while the relative abundance of Clostridium of Ruminococcaceae family was higher in RF-high than in RF-low and RF-negative patients. Among 10 differentially abundant Bifidobacterium, B. longum RAPO exhibited the strongest ability to inhibit IL-17 secretion. Oral administration of B. longum RAPO in CIA mice, obese CIA, and humanized avatar model significantly reduced RA incidence, arthritis score, inflammation, bone damage, cartilage damage, Th17 cells, and inflammatory cytokine secretion. Additionally, B. longum RAPO significantly inhibited Th17 cells and Th17-related genes—IL-17A, IRF4, RORC, IL-21, and IL-23R—in the PBMCs of rheumatoid arthritis patients. Our findings suggest that B. longum RAPO may alleviate RA by inhibiting the production of IL-17 and other proinflammatory mediators. The safety and efficacy of B. longum RAPO in patients with RA and other autoimmune disorders merit further investigation.

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Fibroblasts and mesenchymal cells

Oxford Textbook of Rheumatology ◽

10.1093/med/9780199642489.003.0051 ◽

2013 ◽

pp. 379-385

Author(s):

Andrew Filer ◽

Maria Juarez ◽

Christopher Buckley

Keyword(s):

Rheumatoid Arthritis ◽

Wound Healing ◽

Joint Destruction ◽

Joint Inflammation ◽

Synovial Fibroblasts ◽

Mesenchymal Cells ◽

Structure And Function ◽

Epigenetic Programming ◽

Disease Initiation ◽

And Function

In order to understand and explore the function and roles of fibroblasts, it is necessary to understand their lineage relationships to other mesenchymal cells. Fibroblasts are ubiquitous non-epithelial, non-endothelial, and non-haematopoietic adherent cells that have the capacity to produce and remodel extracellular matrix. In addition to their well-known ’landscaping’ function which determines the unique structure and function of different organs, they play an important role in wound healing, immune tolerance, and disease. In cancer, epithelial-stromal interactions have been implicated in disease initiation and progression. In rheumatoid arthritis, synovial fibroblasts at diseased sites become persistently activated and behave abnormally, orchestrating joint inflammation and contributing to joint destruction. Recent evidence suggests that the activated phenotype of fibroblasts in pathology may result from epigenetic programming, which is becoming a major focus for development of new therapeutics.

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