Effect of electroacupuncture on JAK2/STAT3 pathway in synovial tissues of rats with rheumatoid arthritis

Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis.

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Association ofEMCNwith Susceptibility to Rheumatoid Arthritis in a Japanese Population

The Journal of Rheumatology ◽

10.3899/jrheum.100263 ◽

2010 ◽

Vol 38 (2) ◽

pp. 221-228 ◽

Cited By ~ 5

Author(s):

KAZUMASA NISHIMOTO ◽

KATSUNORI IKARI ◽

HIROTAKA KANEKO ◽

SO TSUKAHARA ◽

YUTA KOCHI ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Association Studies ◽

Functional Study ◽

Positive Staining ◽

Nucleotide Polymorphisms ◽

Data Set ◽

Nuclear Factors ◽

Validation Set ◽

Synovial Tissues ◽

Stratified Analysis

Objective.Endomucin, an endothelial-specific sialomucin, is thought to facilitate “lymphocyte homing” to synovial tissues, resulting in the major histopathologies of rheumatoid arthritis (RA). We examined the association between RA susceptibility and the gene coding endomucin,EMCN.Methods.Association studies were conducted with 2 DNA sample sets (initial set of 1504 patients, 752 controls; and validation set, 1113 patients, 940 controls) using 6 tag single-nucleotide polymorphisms (SNP) from the Japanese HapMap database. Immunohistochemistry for the expression of endomucin was conducted with synovial tissues from 4 patients with RA during total knee arthroplasty. Electromobility shift assays were performed for the functional study of identified polymorphisms.Results.Within the initial sample set, the strongest evidence of an association with RA susceptibility was SNP rs3775369 (OR 1.20, p = 0.0075). While the subsequent replication study did not initially confirm the observed significant association (OR 1.13, p = 0.062), an in-depth stratified analysis revealed significant association in patients testing positive to anti-cyclic citrullinated peptide (anti-CCP) antibody in the replication data set (OR 1.15, p = 0.044). Investigating 2 sample sets, significant associations were detected in overall and stratified samples with anti-CCP antibody status (OR 1.17, p = 0.0015). Positive staining for endomucin was detected in all patients. The allele associated with RA susceptibility had a higher binding affinity for HEK298-derived nuclear factors compared to the nonsusceptible allelic variant of rs3775369.Conclusion.A significant association betweenEMCNand RA susceptibility was detected in our Japanese study population. TheEMCNallele conferring RA susceptibility may also contribute to the pathogenesis of RA.

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Effect of Human Herpesviruses 6 and 7 Infection on the Clinical Course of Rheumatoid Arthritis / Cilvēka Herpesvīrusa 6 Un 7 Infekcijas Ietekme Uz Reimatoīdā Artrīta Klīnisko Gaitu

Proceedings of the Latvian Academy of Sciences Section B Natural Exact and Applied Sciences ◽

10.1515/prolas-2016-0028 ◽

2016 ◽

Vol 70 (4) ◽

pp. 165-174 ◽

Cited By ~ 2

Author(s):

Anda Kadiša ◽

Zaiga Nora-Krūkle ◽

Svetlana Kozireva ◽

Simons Svirskis ◽

Pēteris Studers ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Fluid ◽

Viral Infections ◽

Clinical Course ◽

Immunosuppressive Treatment ◽

Virus Reactivation ◽

Autoimmune Inflammatory Disease ◽

High Prevalence ◽

Synovial Tissues ◽

Infection Markers

Abstract Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease affecting joints and causing symmetrical chronic progressive aseptic synovitis and erosive-destructive changes. Viruses and viral infections are considered to be the main risk factors for autoimmune disease development (especially for individuals with genetic predisposition). The goal of this study was to evaluate the frequency of HHV-6 and HHV-7 persistent infection and its activity phase in RA and osteoarthritis (OA) patients, and healthy persons. We examined also the influence of HHV-6 and -7 infections on RA activity, aggressiveness, radiographical stage, and frequency of complications as well as the presence of HHV-6 infection markers in synovial fluid and synovial tissues of RA joints of affected patients. Despite the lack of significant correlation between frequency of persistent single HHV-6, single HHV-7, and concurrent HHV-6 and HHV-7 infection and RA clinical course, we found that both active and latent HHV-6 and/or HHV-7 infection increased RA activity and progression in several clinical and laboratory parameters. Regarding the severity of the course of RA, we observed also a high prevalence of RA complications in the patient group with active single HHV-6 infection and also a more severe radiographical stage in RA patients with active concurrent HHV-6 and HHV-7 infection. Moreover, viral infection markers were found in synovial fluid and synovial tissues of affected joints of RA patients. This suggests that HHV-6 and/or HHV-7 infection has effect on the disease clinical course, but virus reactivation may be a consequence of immunosuppressive treatment.

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The role of meat in the expression of rheumatoid arthritis

British Journal Of Nutrition ◽

10.1017/s0007114500001926 ◽

2000 ◽

Vol 84 (5) ◽

pp. 589-595 ◽

Cited By ~ 43

Author(s):

William B. Grant

Keyword(s):

Rheumatoid Arthritis ◽

Short Review ◽

Ecological Approach ◽

Statistical Association ◽

Prevalence Data ◽

Statistical Correlations ◽

Period 2 ◽

Dietary Components ◽

Synovial Tissues

Rheumatoid arthritis (RA) is characterized by inflammation of the synovial tissues in the joints. A number of papers related to dietary components that are associated with this inflammation are reviewed. In addition, the ecological approach is used to study the links between diet and RA. Multi-country data for prevalence of RA for females from eight and fifteen countries were compared statistically with components of national dietary supply. Fat from meat and offal for the period 2 years before the prevalence data was found to have the highest statistical association with the prevalence of RA (r2 0·877, P<0·001 for eight countries). The statistical correlations for meat and offal were almost as high as those for their fat. Similar correlations were found for temporal changes in indices of effects of RA in several European countries between 1968 and 1978 as more meat was added to the national diets, although the correlations were higher for meat than for fat. It is hypothesized that meat and offal may be a major factor contributing to the inflammation in RA. In the present short review, the author examines some of the data that associate meat consumption with RA and the possible factors, e.g. fat, Fe and nitrite, which may contribute to the inflammation.

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The levels of leukemia inhibitory factor in synovial tissues of patients with rheumatoid arthritis: inflammation and other proinflammatory cytokines

Modern Rheumatology ◽

10.3109/s10165-002-0210-9 ◽

2003 ◽

Vol 13 (2) ◽

pp. 121-128 ◽

Cited By ~ 4

Author(s):

Hiroyuki Enomoto ◽

Seiji Saito ◽

Hiroshi Yabe ◽

Yoshiaki Toyama ◽

Taisuke Tomatu

Keyword(s):

Rheumatoid Arthritis ◽

Proinflammatory Cytokines ◽

Leukemia Inhibitory Factor ◽

Inhibitory Factor ◽

Synovial Tissues

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Analysis of cell populations in rheumatoid arthritis synovial tissues

Seminars in Arthritis and Rheumatism ◽

10.1016/0049-0172(92)90040-k ◽

1992 ◽

Vol 21 (6) ◽

pp. 393-399 ◽

Cited By ~ 23

Author(s):

Ghada Yanni ◽

Alex Whelan ◽

Conleth Feighery ◽

Barry Bresnihan

Keyword(s):

Rheumatoid Arthritis ◽

Cell Populations ◽

Synovial Tissues

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The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity

Mediators of Inflammation ◽

10.1155/2017/7623145 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 22

Author(s):

Li Zhu ◽

Huaizhou Wang ◽

Yu Wu ◽

Zhengwen He ◽

Yanghua Qin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Synovial Tissue ◽

Active Rheumatoid Arthritis ◽

Synovial Fibroblasts ◽

Serum Levels ◽

Serum Markers ◽

Effector Cells ◽

Joint Replacement Surgery ◽

Replacement Surgery ◽

Synovial Tissues

Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n=20) were significantly higher than those in OA patients (n=16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis.

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