scholarly journals Inhibition of Inflammation and Bone Erosion by RNA Interference-Mediated Silencing of Heterogeneous Nuclear RNP A2/B1 in Two Experimental Models of Rheumatoid Arthritis

2015 ◽  
Vol 67 (9) ◽  
pp. 2536-2546 ◽  
Author(s):  
Sonja Herman ◽  
Anita Fischer ◽  
Jessy Presumey ◽  
Markus Hoffmann ◽  
Marije I. Koenders ◽  
...  
Autoimmunity ◽  
2010 ◽  
Vol 43 (8) ◽  
pp. 642-653 ◽  
Author(s):  
Cheng-Chi Chao ◽  
Shi-Juan Chen ◽  
Iannis E. Adamopoulos ◽  
Michael Judo ◽  
Agelio Asio ◽  
...  

Autoimmunity ◽  
2010 ◽  
Vol 44 (3) ◽  
pp. 243-252 ◽  
Author(s):  
Cheng-Chi Chao ◽  
Shi-Juan Chen ◽  
Iannis E. Adamopoulos ◽  
Nicole Davis ◽  
Kyu Hong ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Larissa Lumi Watanabe Ishikawa ◽  
Priscila Maria Colavite ◽  
Larissa Camargo da Rosa ◽  
Bianca Balbino ◽  
Thais Graziela Donegá França ◽  
...  

Rheumatoid arthritis (RA) is the most common systemic autoimmune disease. It affects mainly the joints, causing synovitis, cartilage destruction, and bone erosion. Many experimental models are used to study the mechanisms involved in immunopathogenesis and new therapies for this disease. Proteoglycan-induced arthritis (PGIA) is a widely used model based on the cross-reactivity of injected foreign (usually human) PG and mice self-PG. Considering the complexity of the extraction and purification of human PG, in this study we evaluated the arthritogenicity of bovine PG that is commercially available. Bovine PG was highly arthritogenic, triggering 100% incidence of arthritis in female BALB/c retired breeder mice. Animals immunized with bovine PG presented clinical symptoms and histopathological features similar to human RA and other experimental models. Moreover, bovine PG immunization determined higher levels of proinflammatory and anti-inflammatory cytokines in arthritic mice compared to healthy ones. As expected, only the arthritic group produced IgG1 and IgG2a antibodies against PG. Thus, commercial bovine PG can be used as an alternative antigenic source to PGIA for the study of many RA aspects, including the immunopathogenesis of the disease and also the development of new therapies.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 695
Author(s):  
Javier Conde ◽  
Isabel Fernández-Pisonero ◽  
Myriam Cuadrado ◽  
Antonio Abad ◽  
Javier Robles-Valero ◽  
...  

Genetic evidence suggests that three members of the VAV family (VAV1, VAV2 and VAV3) of signal transduction proteins could play important roles in rheumatoid arthritis. However, it is not known currently whether the inhibition of these proteins protects against this disease and, if so, the number of family members that must be eliminated to get a therapeutic impact. To address this issue, we have used a collection of single and compound Vav family knockout mice in experimental models for antigen-dependent (methylated bovine serum albumin injections) and neutrophil-dependent (Zymosan A injections) rheumatoid arthritis in mice. We show here that the specific elimination of Vav1 is sufficient to block the development of antigen-induced arthritis. This protection is likely associated with the roles of this Vav family member in the development and selection of immature T cells within the thymus as well as in the subsequent proliferation and differentiation of effector T cells. By contrast, we have found that depletion of Vav2 reduces the number of neutrophils present in the joints of Zymosan A-treated mice. Despite this, the elimination of Vav2 does not protect against the joint degeneration triggered by this experimental model. These findings indicate that Vav1 is the most important pharmacological target within this family, although its main role is limited to the protection against antigen-induced rheumatoid arthritis. They also indicate that the three Vav family proteins do not play redundant roles in these pathobiological processes.


2021 ◽  
Vol 22 (5) ◽  
pp. 2426
Author(s):  
Askhat Myngbay ◽  
Limara Manarbek ◽  
Steve Ludbrook ◽  
Jeannette Kunz

Rheumatoid arthritis (RA) is a chronic autoimmune disease causing inflammation of joints, cartilage destruction and bone erosion. Biomarkers and new drug targets are actively sought and progressed to improve available options for patient treatment. The Collagen Triple Helix Repeat Containing 1 protein (CTHRC1) may have an important role as a biomarker for rheumatoid arthritis, as CTHRC1 protein concentration is significantly elevated in the peripheral blood of rheumatoid arthritis patients compared to osteoarthritis (OA) patients and healthy individuals. CTHRC1 is a secreted glycoprotein that promotes cell migration and has been implicated in arterial tissue-repair processes. Furthermore, high CTHRC1 expression is observed in many types of cancer and is associated with cancer metastasis to the bone and poor patient prognosis. However, the function of CTHRC1 in RA is still largely undefined. The aim of this review is to summarize recent findings on the role of CTHRC1 as a potential biomarker and pathogenic driver of RA progression. We will discuss emerging evidence linking CTHRC1 to the pathogenic behavior of fibroblast-like synoviocytes and to cartilage and bone erosion through modulation of the balance between bone resorption and repair.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 876.2-877
Author(s):  
S. Tsujimoto ◽  
M. Shigesaka ◽  
A. Tanaka ◽  
Y. Ozaki ◽  
T. Ito ◽  
...  

Background:Rheumatoid arthritis (RA) is a common autoimmune disease. It is characterized by systemic synovitis with bone erosion and joint cartilage degradation(1). Production of autoantibody is important for autoimmune disease. Cytokines play crucial roles in its pathogenesis(2). SNP distribution varies between races. Few studies have examined SNP targeted at Japanese patients. The analysis of cytokine gene polymorphisms is important factor of pathophysiology and treatment.Objectives:This analysis was aimed to investigate the association between cytokine gene polymorphisms and autoantibody and therapeutic response in Japanese RA patients.Methods:This study subjects consisted of 100 RA patients and 50 healthy controls. We extracted data on patient sex, age, disease duration, rheumatoid factor (RF), anti cyclic citrullinated peptide (anti-CCP) antibody and therapeutic response including methotrexate (MTX) and biological DMARDs. Genomic DNA was isolated from peripheral blood, these were genotyped for TNFα, TGFβ1, IL-6, IL-10 and IFNγ polymorphisms. We analyzed these data using a chi-square test.Results:IL-10 (-819 C/T and -592 C/A) revealed that there were significant decrease in the frequency of IL-10 (-819) CC genotype and (-592) CC genotype as compared to controls in RA patients. Genotyping of IL-10 showed that there was significant decrease ACC/ACC genotype (Table 1).IFNγ (+874 A/T) revealed that there was significant decrease in the frequency of TT genotype as compared to controls (Table 1).No significant differences in TNFα, TGFβ1and IL-6 genotypes and alleles frequency were observed between RA patients and control.TGFβ1(+869 A/T) in patients with anti-CCP antibody positive revealed that there was significant decrease in the frequency of TT genotype as compared to patients with anti-CCP antibody negative (Table 2).No significant association between RF and any cytokine gene polymorphism.Analyzing cytokine gene polymorphisms could be useful for treatment with MTX and biological DMARDs.Table 1.Table 2.Conclusion:IL-10 (-819 C/T, -592 C/A) and IFNγ (+874 A/T) polymorphism might be related to RA in Japanese population. In addition, TGFβ1(+869 A/T) polymorphism might be associated with the production of anti-CCP antibody. These results suggest that the analyzing cytokine gene polymorphisms may offer promise as useful factors in the choice of treatment for Japanese RA patients.References:[1] Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet. 2010; 376: 1094–108.[2] McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007 Jun;7(6):429-42.Disclosure of Interests:None declared


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 772
Author(s):  
Alessia Alunno ◽  
Francesco Carubbi ◽  
Elena Bartoloni ◽  
Davide Grassi ◽  
Claudio Ferri ◽  
...  

In recent years, an increasing interest in the influence of diet in rheumatic and musculoskeletal diseases (RMDs) led to the publication of several articles exploring the role of food/nutrients in both the risk of developing these conditions in normal subjects and the natural history of the disease in patients with established RMDs. Diet may be a possible facilitator of RMDs due to both the direct pro-inflammatory properties of some nutrients and the indirect action on insulin resistance, obesity and associated co-morbidities. A consistent body of research has been conducted in rheumatoid arthritis (RA), while studies in systemic lupus erythematosus (SLE) are scarce and have been conducted mainly on experimental models of the disease. This review article aims to outline similarities and differences between RA and SLE based on the existing literature.


2018 ◽  
Vol 45 (7) ◽  
pp. 895-904 ◽  
Author(s):  
Ying-Qian Mo ◽  
Ze-Hong Yang ◽  
Hai-Ning He ◽  
Jian-Da Ma ◽  
Jin-Jian Liang ◽  
...  

Objective.To explore the advantages of magnetic resonance imaging (MRI) of bilateral hands in rheumatoid arthritis (RA).Methods.Consecutive patients with active RA were recruited for clinical assessments, radiographs, and MRI of bilateral hands. Bilateral hands were scanned simultaneously on 3.0 T whole-body MRI system and were scored on synovitis, osteitis, and bone erosion according to the RA MRI scoring (RAMRIS) system.Results.Among 120 patients included, wrist bones and metacarpophalangeal joint (MCPJ) 2 proximal showed bone erosion in early RA. The second to fifth metacarpal bases and the second to fourth MCPJ distal showed more bone erosion in mid-stage or late-stage RA. When MRI of dominant unilateral hand was analyzed, MRI synovitis and osteitis in 5% of wrists and 3 MRI features in 5–14% of MCPJ were misdiagnosed (McNemar test, all p < 0.05). There were 46% wrist synovitis, 29–52% MCPJ2–5 synovitis, 45% wrist osteitis, and 20%–34% MCPJ2–5 osteitis not detected by joint tenderness and/or swelling. When the clinically more severe hand was selected for MRI of unilateral hand according to physical examination, MRI synovitis in 5% of wrists and 3 MRI features in 7–15% of MCPJ were misdiagnosed (all p < 0.05). Scatter plots and linear regression analyses were used to illustrate RAMRIS between dominant or selected hand (Y values) and nondominant or nonselected hand (X values). All linear models were markedly different from a Y = X linear model, indicating the dominant or clinically more severe hand could not represent the contralateral hand to evaluate RAMRIS.Conclusion.MRI of bilateral hands is more optimal than MRI of the unilateral hand in RA.


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