scholarly journals Pathogenesis and Function of Interleukin-35 in Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Pan Lin Xin ◽  
Li Fan Jie ◽  
Qian Cheng ◽  
Du Yi Bin ◽  
Cheng Wen Dan
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cell ◽  
T Regulatory Cells ◽  
Therapeutic Potential ◽  
Bone Destruction ◽  
Pathological Process ◽  
Interleukin 12 ◽  
Synovial Hyperplasia ◽  
And Function ◽  
Anti Inflammatory Cytokine

It is well known that RA (Rheumatoid arthritis) is an autoimmune disease characterized by multiple and symmetric arthropathy. The main pathological features of RA are synovial hyperplasia, angiogenesis, pannus formation, inflammatory cell infiltration, articular cartilage, bone destruction, and ultimately joint dysfunction, even deformity. IL-35 (Interleukin-35) is a new member of the IL-12 (Interleukin-12) family, which is an immunosuppressive and anti-inflammatory cytokine secreted mainly by Treg (T regulatory cells). There is evidence suggested that IL-35 can attenuate the progression of RA through influencing the immune and pathological process. It suggests that IL-35 played an important role in the pathogenesis of RA, and can be used as a potential target for the future treatment of RA. This review summarizes the recent advances of IL-35 in the pathological roles and the therapeutic potential roles in RA.

Advancement of Natural Compounds as Anti- Rheumatoid Arthritis Agents: Focus on Their Mechanism of Actions

2021 ◽  
Vol 21 ◽  
Author(s):  
Huanghe Yu ◽  
Yixing Qiu ◽  
Shumaila Tasneem ◽  
Muhammad Daniyal ◽  
Bin Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Molecular Mechanisms ◽  
Bone Destruction ◽  
Inflammatory Cells ◽  
Chronic Inflammatory Disease ◽  
Mechanisms Of Action ◽  
Pannus Formation ◽  
Synovial Hyperplasia ◽  
Naturally Occurring ◽  
Natural Plants

: Rheumatoid arthritis (RA) is a chronic inflammatory disease categorized by infiltration of inflammatory cells, synovial hyperplasia, pannus formation and bone destruction, leading to disability worldwide. Despite the presence of the commercial availability of anti-RA agent on the market, the application of these drugs is limited due to its side effects. Anti-rheumatic drugs are more effective and safer being investigated by many researchers, especially, natural products with anti-RA have been identified and the underlying molecular mechanisms of action of novel and known compounds have been reported. In this review, we intend to provide a comprehensive view and updated on naturally occurring compounds known and novel that has the effect of anti-RA, and then classify them according to their molecular mechanisms of action in regulating the anti-RA lane main. The safety of compounds from natural plants and western medicine has also been briefly compared. In addition, the clinical trials with anti-RA compounds isolated from natural plants in RA were also summarized in this manuscript.

scholarly journals Repurposing of Pirfenidone (Anti-Pulmonary Fibrosis Drug) for Treatment of Rheumatoid Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Donghao Gan ◽  
Wenxiang Cheng ◽  
Liqing Ke ◽  
Antonia RuJia Sun ◽  
Qingyun Jia ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Chondrocytes ◽  
Joint Destruction ◽  
Pathological Process ◽  
Therapeutic Drug ◽  
Pathological Changes ◽  
Synovial Hyperplasia ◽  
Tnf Α ◽  
And Migration

Clinical studies have shown that pirfenidone (PFD) effectively relieves joint pain in rheumatoid arthritis (RA) patients. However, the detailed mechanisms underlying the anti-RA effects of PFD have not been investigated. This study was undertaken to investigate the repurposing of PFD for the treatment of RA, and explore its anti-rheumatic mechanisms. A collagen-induced arthritis (CIA) rat model was used to observe joint pathological changes following PFD treatment. Based on bioinformatics to predict the mechanism of PFD anti-RA, using EA. hy926 and TNF-α-induced MH7A cells to establish in vitro model to explore its biological mechanism from the perspectives of synovial inflammation and angiogenesis. PFD significantly relieved pathological changes, including joint swelling, synovial hyperplasia, inflammatory cell infiltration and joint destruction. PFD was also associated with reduced expression of MMP-3 and VEGF in articular chondrocytes and synovial cells of CIA rats (p < 0.05). Using bioinformatic methods, we predicted that PFD inhibits cell inflammation and migration by interfering with the JAK2/STAT3 and Akt pathways. These results were verified using in vitro models. In particular, PFD effectively reduced the expression of pro-inflammatory, chondrogenic, and angiogenic cytokines, such as IL-1β, IL-6, IL-8, MMP-1/3/2/9 and VEGF (p < 0.05), in TNF-α-induced MH7A cells. In addition, PFD significantly reduced the production of MMP-2/9 and VEGF in EA. hy926 cells, thereby weakening migration and inhibiting angiogenesis (p < 0.05). These findings suggest that PFD may alleviate the pathological process in CIA rats, by inhibiting inflammation and angiogenesis through multiple pathways, and serve as a potential therapeutic drug for RA.

Dynamics of lymphocyte subpopulations, CD4+CD25+CD127- T regulatory cells in patients with rheumatoid arthritis during therapy with the rituximab biosimilar Acellbia

2020 ◽  
Vol 14 (2) ◽  
pp. 20-26
Author(s):  
A. S. Avdeeva ◽  
Yu. P. Rubtsov ◽  
M. V. Cherkasova ◽  
E. L. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Pathological Process ◽  
Blood Levels ◽  
Moderate Activity ◽  
Regulatory Cells ◽  
Flow Cytofluorometry ◽  
Reactive Protein ◽  
Das28 Remission

Objective: to evaluate the effect of the rituximab (RTM) biosimilar Acellbia on the peripheral blood levels of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, and CD4+CD25+CD127- lymphocytes in patients with rheumatoid arthritis (RA).Patients and methods. Examinations were made in 20 RA patients who received 2 RTM infusions at a total dose of 1200 mg. The levels of C-reactive protein, IgM rheumatoid factor, IgG, IgM, and IgA were measured by a nephelometric method. The relative and absolute contents of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, CD4+CD25+CD127- T regulatory cells (Tregs) were estimated by multicolor flow cytofluorometry.Results and discussion. At week 24 of RTM therapy, there was a good/satisfactory effect according to EULAR criteria in 17 (85%) patients; DAS28 remission in 4 (20%), and SDAI remission in 2 (10%). The use of RTM was accompanied by a significant increase in the relative content of CD4+CD25+CD127- T lymphocytes, the median of which at weeks 12 and 24 after therapy initiation increased from 6.8 [5.2; 7.6]% to 7.3 [6.1; 8.3] and 6.97 [6.4; 8.2]%, respectively (p<0.05). The absolute peripheral blood count of Tregs tended to increase at weeks 12 after the first infusion of the drug (up to 0.05 [0.04; 0.075] ⋅ 109 /l; p=0.05). At week 24 follow-up, the patients who achieved SDAI remission/low disease activity had significantly higher baseline relative Tregs levels (7.35 [6.8; 7.97]% than those with the moderate activity of the pathological process (5.8 [4.3; 7.22] %; p<0.05).Conclusion. The use of the RTM biosimilar is accompanied by the development of complete depletion of CD19+ lymphocytes and by an increase in CD3+ and CD3+CD4+ lymphocytes and Tregs. The larger baseline number of CD4+CD25+CD127- lymphocytes is associated with the higher efficiency of RTM therapy.

scholarly journals Baihu Jia Guizhi Decoction Improves Rheumatoid Arthritis Inflammation by Regulating Succinate/SUCNR1 Metabolic Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Huan Chen ◽  
Ting Pan ◽  
Panwang Liu ◽  
Ping Wang ◽  
Shijun Xu
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cell ◽  
Underlying Mechanism ◽  
Synovial Hyperplasia ◽  
Guizhi Decoction ◽  
Metabolic Signal ◽  
Anemarrhena Asphodeloides ◽  
Stimulation Of ◽  
Inflammatory Effect

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Succinate is an inflammatory metabolic signal that exacerbates RA synovitis by activating succinate receptor 1 (SUCNR1) to amplify the release of IL-1β. Thus, inhibition of succinate activation of SUCRN1 could be an effective method to inhibit the inflammation of RA. Baihu Jia Guizhi decoction (BHGZ), which is composed of Gypsum Fibrosum, Anemarrhena asphodeloides Bge., Cinnamomum cassia Presl., Glycyrrhiza uralensis Fisch., and Oryza sativa L., is a Traditional Chinese Medicine (TCM) prescription used to treat RA in clinic. In addition, TCM believes that damp and heat environment is one of the causes of RA. In this study, we tested the role of damp and heat environments in exacerbating RA inflammation and the anti-inflammatory effect of BHGZ, based on succinate/SUCNR1/IL-1β pathway in the adjuvant arthritis (AA) model with damp and heat environment (AA + DHE). Results showed that paw swelling and synovial pathology were significantly increased in AA rats, and these results were aggravated by stimulation in damp and heat environment. BHGZ improved AA + DHE rats’ paw swelling, synovial hyperplasia, and inflammatory cell infiltration and reduced IL-1β. In addition, AA rats significantly increased the expression of SUCNR1, and the stimulation of damp and heat environment not only increased the expression of SUCNR1 but also promoted the accumulation of succinate. BHGZ simultaneously reduced the concentration of succinate and the expression of SUCNR1. Finally, SDH activity was decreased in AA rats and AA + DHE rats, while BHGZ increased SDH activity and then reduced succinate concentration. Therefore, we prove that damp and heat environment deteriorated the inflammation of RA which is the activation of succinate/SUCNR1 pathway, while BHGZ regulates SDH activity to reduce the accumulation of succinate and inhibit the activation of SUCNR1 that is the underlying mechanism of its treatment of RA.

scholarly journals Acid-Sensing Ion Channel-1a in Articular Chondrocytes and Synovial Fibroblasts: A Novel Therapeutic Target for Rheumatoid Arthritis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yayun Xu ◽  
Feihu Chen
Keyword(s):  
Rheumatoid Arthritis ◽  
Articular Cartilage ◽  
Ion Channel ◽  
Articular Chondrocytes ◽  
Distribution Channel ◽  
Bone Destruction ◽  
Synovial Fibroblasts ◽  
Synovial Inflammation ◽  
And Function ◽  
Chronic Autoimmune Disease

Acid-sensing ion channel 1a (ASIC1a) is a member of the extracellular H+-activated cation channel family. Emerging evidence has suggested that ASIC1a plays a crucial role in the pathogenesis of rheumatoid arthritis (RA). Specifically, ASIC1a could promote inflammation, synovial hyperplasia, articular cartilage, and bone destruction; these lead to the progression of RA, a chronic autoimmune disease characterized by chronic synovial inflammation and extra-articular lesions. In this review, we provided a brief overview of the molecular properties of ASIC1a, including the basic biological characteristics, tissue and cell distribution, channel blocker, and factors influencing the expression and function, and focused on the potential therapeutic targets of ASIC1a in RA and possible mechanisms of blocking ASIC1a to improve RA symptoms, such as regulation of apoptosis, autophagy, pyroptosis, and necroptosis of articular cartilage, and synovial inflammation and invasion of fibroblast-like cells in synovial tissue.

scholarly journals Multi-omics Analysis of the Biomarkers and Molecular Mechanism of Rheumatoid Arthritis With Bone Destruction

2021 ◽  
Author(s):  
Qian Huang ◽  
Jiang Su ◽  
Weihua Zhang ◽  
Shengjia Chang ◽  
Silin Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
16S Rrna ◽  
Bone Destruction ◽  
Gut Bacteria ◽  
Plasma Metabolites ◽  
Healthy Control ◽  
Novel Biomarkers ◽  
Bacteria And Fungi ◽  
And Function

Abstract ObjectivesOur study aimed to elucidate the role of metabolites, bacteria, and fungi in rheumatoid arthritis (RA) patients with bone destruction (BD(+)) and find some biomarkers to predicate bone progression of RA.MethodsWe conducted plasma metabolites of the 127 RA patients and 69 healthy control by using nontargeted liquid chromatography-mass spectrometry (LC-MS), and the gut bacteria and fungi were assessed by 16S rRNA and internal transcribed spacer (ITS).ResultsCompared with RA patients without bone destruction (BD(-)), some metabolites, bacteria, and fungi altered in BD(+). Sever metabolites were selected as key metabolites for classifying the BD(+) and BD(-) groups with moderate accuracy (AUC=0.71). Metabolites-groups, metabolites-metabolites, and metabolites-clinical factors had a certain correlation, and 7 metabolites were enriched in glycerophospholipid metabolism and L-arginine and proline metabolism pathways. The bacteria and fungi of the BD(+) group showed significant differences in composition and function compared with BD(-) group. The changed 4 bacteria and 12 fungi yielded accuracy (AUC=0.74 and AUC=0.87, respectively) for the two groups. Taken 7 metabolites, 4 bacteria and 12 fungi as a panel for AUC analysis, an improved AUC of 0.99 significantly discriminated the two groups. The changed metabolites, gut bacteria, and fungi may affected the pathway related to L-arginine.ConclusionsOur nontargeted LC-MS, 16S rRNA, and ITS highlight a novel link among the metabolites, bacteria, fungi, and pathology of BD(+), which contributed to our understanding of the role of metabolites, bacteria, and fungi in BD(+) aetiology and offers some novel biomarkers to predict the bone progression of RA.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Rheumatoid Arthritis

2021 ◽  
Vol 22 (21) ◽  
pp. 11592
Author(s):  
Madina Sarsenova ◽  
Assel Issabekova ◽  
Saule Abisheva ◽  
Kristina Rutskaya-Moroshan ◽  
Vyacheslav Ogay ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Stem Cell ◽  
Bone Destruction ◽  
Autoimmune Disorder ◽  
Promising Tool ◽  
Cell Based Therapy ◽  
And Function ◽  
Preclinical And Clinical Studies ◽  
Adaptive Immune Systems

Mesenchymal stem cells (MSCs) have great potential to differentiate into various types of cells, including but not limited to, adipocytes, chondrocytes and osteoblasts. In addition to their progenitor characteristics, MSCs hold unique immunomodulatory properties that provide new opportunities in the treatment of autoimmune diseases, and can serve as a promising tool in stem cell-based therapy. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that deteriorates quality and function of the synovium membrane, resulting in chronic inflammation, pain and progressive cartilage and bone destruction. The mechanism of RA pathogenesis is associated with dysregulation of innate and adaptive immunity. Current conventional treatments by steroid drugs, antirheumatic drugs and biological agents are being applied in clinical practice. However, long-term use of these drugs causes side effects, and some RA patients may acquire resistance to these drugs. In this regard, recently investigated MSC-based therapy is considered as a promising approach in RA treatment. In this study, we review conventional and modern treatment approaches, such as MSC-based therapy through the understanding of the link between MSCs and the innate and adaptive immune systems. Moreover, we discuss recent achievements in preclinical and clinical studies as well as various strategies for the enhancement of MSC immunoregulatory properties.

scholarly journals Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2627
Author(s):  
Chien-Chung Huang ◽  
Yat-Yin Law ◽  
Shan-Chi Liu ◽  
Sung-Lin Hu ◽  
Jun-An Lin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Progenitor Cell ◽  
Progenitor Cell ◽  
Therapeutic Potential ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Synovial Cell ◽  
Vegf Expression ◽  
Endothelial Progenitor

Rheumatoid arthritis (RA) is an erosive polyarthritis that can lead to severe joint destruction and painful disability if left untreated. Angiogenesis, a critical pathogenic mechanism in RA, attracts inflammatory leukocytes into the synovium, which promotes production of proinflammatory cytokines and destructive proteases. Adipokines, inflammatory mediators secreted by adipose tissue, also contribute to the pathophysiology of RA. The most abundant serum adipokine is adiponectin, which demonstrates proinflammatory effects in RA, although the mechanisms linking adiponectin and angiogenic manifestations of RA are not well understood. Our investigations with the human MH7A synovial cell line have revealed that adiponectin dose- and time-dependently increases vascular endothelial growth factor (VEGF) expression, stimulating endothelial progenitor cell (EPC) tube formation and migration. These adiponectin-induced angiogenic activities were facilitated by MEK/ERK signaling. In vivo experiments confirmed adiponectin-induced downregulation of microRNA-106a-5p (miR-106a-5p). Inhibiting adiponectin reduced joint swelling, bone destruction, and angiogenic marker expression in collagen-induced arthritis (CIA) mice. Our evidence suggests that targeting adiponectin has therapeutic potential for patients with RA. Clinical investigations are needed.

scholarly journals α-Mangostin Inhibits LPS-Induced Bone Resorption by Restricting Osteoclastogenesis Via NF-κB and MAPK Signaling

2021 ◽  
Author(s):  
Wenkan Zhang ◽  
guangyao Jiang ◽  
xiaozhong zhou ◽  
leyi huang ◽  
jiahong meng ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Therapeutic Potential ◽  
Bone Destruction ◽  
Mapk Signaling ◽  
Osteoclast Formation ◽  
Receptor Activator ◽  
Cardioprotective Effects ◽  
And Function

Abstract Background: Excessive activation of osteoclasts is an important cause of imbalance in bone remodeling, which further leads to pathological bone destruction. This is a clear feature of many osteolytic diseases, such as rheumatoid arthritis, osteoporosis, and osteolysis around the prosthesis. Based on the fact that many natural compounds have therapeutic potential for treating these diseases by suppressing osteoclast formation and function, we proved that α-mangostin, a natural compound isolated from mango, might be a promising choice. α-mangostin was described had anti‐inflammatory, anticancer and cardioprotective effects. Methods: We evaluated the therapeutic effect of α-mangostin in the process of osteoclast formation and bone resorption. The receptor activator of NF-κB ligand (RANKL) induces the formation of osteoclasts in vitro, and the potential pathways of α-mangostin to inhibit the differentiation and function of osteoclasts were explored. A mouse model of LPS‐induced calvarial osteolysis was establish. Subsequently, micro-CT, histology, etc. were used to evaluate the effect of α-mangostin in preventing inflammatory osteolysis.Results: In our study, we found that α-mangostin could inhibit RANKL-induced osteoclastogenesis and reduced osteoclast‐related gene expression in vitro. Besides, F-actin ring immunofluorescence and resorption pit assay indicated that α-mangostin can also destroy the function of osteoclast. Furthermore, α-mangostin achieved these effects by disrupting the activation of NF-κB/MAPKs signaling pathways. In vivo, our data revealed that α-mangostin could protect mouse calvarial from osteolysis. Conclusions: Together, our study demonstrates that α-mangostin exhibit the ability of inhibiting steoclastogenesis both in vitro and in vivo, and may be a potential option for treating osteoclast‐related diseases.

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