scholarly journals The role of meat in the expression of rheumatoid arthritis

2000 ◽  
Vol 84 (5) ◽  
pp. 589-595 ◽  
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.

scholarly journals METTL3 Promotes Activation and Inflammation of FLSs Through the NF-κB Signaling Pathway in Rheumatoid Arthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Wen Shi ◽  
Yan Zheng ◽  
Shuai Luo ◽  
Xiaofeng Li ◽  
Yilong Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Vital Role ◽  
Experimental Results ◽  
Invasion And Migration ◽  
Crucial Component ◽  
Synovial Tissues ◽  
And Migration

Rheumatoid arthritis (RA), a common autoimmune disease, is extremely damaging to human health. Fibroblast-like synoviocytes (FLSs) have a vital role in the occurrence and development of RA. Methyltransferase-like 3 (METTL3), which is a crucial component of the N6-methyladenosine (m6A) methyltransferase complex, is involved in the progression of many diseases. In this study, we explored the role of METTL3 in the inflammatory response and proliferation, invasion, and migration of FLSs. We used human RA synovial tissues and the adjuvant-induced arthritis (AIA) animal model of RA. Experimental results revealed that METTL3 expression was significantly upregulated in human RA synovial tissues and in the rat AIA model. METTL3 knockdown suppressed interleukin (IL)-6, matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs. In contrast, they were increased by METTL3 overexpression. Additionally, we found that, in FLSs, METTL3 may activate the nuclear factor (NF)-κB signaling pathway. The experimental results showed that METTL3 may promote FLS activation and inflammatory response via the NF-κB signaling pathway.

The Protective Role of Inhibition of Keratin on Rheumatoid Arthritis

2019 ◽  
Vol 9 (6) ◽  
pp. 797-803
Author(s):  
Yan Zhao ◽  
Lanxiu Yang ◽  
Jihong Pan ◽  
Huan Zhang ◽  
Guodong Sun ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometric Analysis ◽  
Protective Role ◽  
Invasion And Migration ◽  
Flow Cytometric ◽  
Migratory Capacity ◽  
Synovial Tissues ◽  
And Migration ◽  
Fibroblast Like Synoviocytes

Objective: Rheumatoid arthritis (RA) is a common inflammatory disease. Studies showed that keratin type II cuticular Hb4 (KRT84) was highly expressed in the synovial membrane of patients with RA. However, the function and mechanism of KRT84 in RA is still unclear. Methods: In this study, we isolated fibroblast-like synoviocytes (FLS) from the mixed knee joint synovial tissues from five patients with RA and the cells were treated with KRT84 siRNA. After transfection of 24 h and 36 h, the knockdown efficiency and expression of relevant genes was detected by RT-PCR. MTT assay, transwell assay, wound scratch assays, flow cytometric analysis and ELISA were used to assess cell proliferation, invasive and migratory capacity. Results: We found that the invasion and migration of RAFLS were significantly decreased after transfection of KRT84 siRNA. ELISA showed a remarkably decrease in TNF-α secretion after KRT84 knockdown. We also explore stimulatory factors for high expression of KRT84 in RA. The inhibitors of ERK, STAT3 and NF-κ B pathways were employed. Our results showed that the expression of KRT84 in RAFLS was evidently increased after treatment with ERK and STAT3 pathway inhibitor. Conclusions: These results imply a protective role of KRT84 knockdown on RA and lay a foundation for further studies on the pathogenetic mechanisms of RA.

scholarly journals RANTES and Chemotactic Activity in Synovial Fluids From Patients With Rheumatoid Arthritis and Osteoarthritis

2005 ◽  
Vol 2005 (6) ◽  
pp. 343-348 ◽  
Author(s):  
Joanna Stanczyk ◽  
Marek L. Kowalski ◽  
Janina Grzegorczyk ◽  
Barbara Szkudlinska ◽  
Marzanna Jarzebska ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Biochemical Analysis ◽  
Mononuclear Cells ◽  
Inflammatory Cells ◽  
Chemotactic Activity ◽  
Pathological Feature ◽  
Potential Mediator ◽  
Synovial Tissues ◽  
Massive Accumulation

A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62±12and24±6cells/HPF, resp) as compared to patients with OA (23±6;P<.05and6±2cells/HPF;P<0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145±36pg/mL), while OA SF was characterised by only trace amount of this chemokine (2±1pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA+MoCA;R=0.61;P<.05). Surprisingly, RANTES correlated also positively with neutrophiles number (R=0.77;P<0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and composition of cellular infiltration in joints affected with inflammatory arthritis.

scholarly journals Differential inflammation-mediated function of prokineticin 2 in the synovial fibroblasts of patients with rheumatoid arthritis compared to osteoarthritis

2021 ◽  
Author(s):  
Kentaro Noda ◽  
Bianca Dufner ◽  
Haruyasu Ito ◽  
Ken Yoshida ◽  
Gianfranco Balboni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Sickness Behaviors ◽  
Synovial Tissues ◽  
Fibroblast Like Synoviocytes

Abstract Prokineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and the circadian rhythm. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, whether PK2 influences the pathogenesis of rheumatoid arthritis (RA) or osteoarthritis (OA) remains unknown. In this study, we collected synovial tissue, plasma, synovial fluid, and fibroblast-like synoviocytes (FLS) from RA and OA patients to analyze the role of PK2 using immunohistochemistry, ELISAs, and tissue superfusion studies. PK2 and its receptors prokineticin receptor (PKR) 1 and 2 were expressed in RA and OA synovial tissues. PKR1 expression in RA synovial tissue was downregulated compared with OA synovial tissue. The PK2 concentration was higher in RA synovial fluid than in OA synovial fluid but similar between RA and OA plasma. PK2 suppressed the production of IL-6 from TNFα-prestimulated OA-FLS, and this effect was attenuated in TNFα-prestimulated RA-FLS. This phenomenon was accompanied by the upregulation of PKR1 in OA-FLS and the downregulation of PK2 and PKR1 in RA-FLS. This study provides a new model to explain some aspects underlying the chronicity of inflammation in RA.

scholarly journals Differential inflammation-mediated function of prokineticin 2 in the synovial fibroblasts of patients with rheumatoid arthritis compared with osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kentaro Noda ◽  
Bianca Dufner ◽  
Haruyasu Ito ◽  
Ken Yoshida ◽  
Gianfranco Balboni ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Synovial Tissue ◽  
Synovial Fibroblasts ◽  
Collagen Induced Arthritis ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Sickness Behaviors ◽  
Synovial Tissues

AbstractProkineticin 2 (PK2) is a secreted protein involved in several pathological and physiological processes, including the regulation of inflammation, sickness behaviors, and circadian rhythms. Recently, it was reported that PK2 is associated with the pathogenesis of collagen-induced arthritis in mice. However, the role of PK2 in the pathogenesis of rheumatoid arthritis (RA) or osteoarthritis (OA) remains unknown. In this study, we collected synovial tissue, plasma, synovial fluid, and synovial fibroblasts (SF) from RA and OA patients to analyze the function of PK2 using immunohistochemistry, enzyme-linked immunosorbent assays, and tissue superfusion studies. PK2 and its receptors prokineticin receptor (PKR) 1 and 2 were expressed in RA and OA synovial tissues. PKR1 expression was downregulated in RA synovial tissue compared with OA synovial tissue. The PK2 concentration was higher in RA synovial fluid than in OA synovial fluid but similar between RA and OA plasma. PK2 suppressed the production of IL-6 from TNFα-prestimulated OA-SF, and this effect was attenuated in TNFα-prestimulated RA-SF. This phenomenon was accompanied by the upregulation of PKR1 in OA-SF. This study provides a new model to explain some aspects underlying the chronicity of inflammation in RA.

scholarly journals CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis

2019 ◽  
Vol 78 (12) ◽  
pp. 1632-1641 ◽  
Author(s):  
Guanhua Song ◽  
Tingting Feng ◽  
Ru Zhao ◽  
Qiqi Lu ◽  
Yutao Diao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Response ◽  
Osteoclast Differentiation ◽  
Small Interfering Rnas ◽  
Inflammatory Stimuli ◽  
Synovial Tissues ◽  
Factor Α ◽  
Fibroblast Like Synoviocytes

ObjectiveThe aim of this study was to investigate the role of CD109 in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and to evaluate its potential as a therapeutic target.MethodsCD109 expression was examined in synovial tissues and FLSs from RA patients and collagen-induced arthritis (CIA) model mice. CD109-deficient mice were developed to evaluate the severity of CIA. Small interfering RNAs and a neutralising antibody against CD109 (anti-CD109) were designed for functional or treatment studies in RA FLSs and CIA.ResultsCD109 was found to be abundantly expressed in the synovial tissues from RA patients and CIA mice. CD109 expression in RA FLSs was upregulated by inflammatory stimuli, such as interleukin-1β and tumour necrosis factor-α. Silencing of CD109 or anti-CD109 treatment reduced proinflammatory factor production, cell migration, invasion, chemoattractive potential and osteoclast differentiation, thereby reducing the deleterious inflammatory response of RA FLSs in vitro. Mice lacking CD109 were protected against arthritis in the CIA model. Anti-CD109 treatment prevented the onset and ameliorated the severity of CIA lesions.ConclusionOur study uncovers an antiarthritic role for CD109 and suggests that CD109 inhibition might serve as a promising novel therapeutic strategy for RA.

scholarly journals Shedding New Light on The Role of ανβ3 and α5β1 Integrins in Rheumatoid Arthritis

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1537 ◽  
Author(s):  
Arwa Morshed ◽  
Abdul Baset Abbas ◽  
Jialiang Hu ◽  
Hanmei Xu
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Vessels ◽  
Biological Effects ◽  
Cell Communication ◽  
Inflammatory Factors ◽  
Synovial Tissues ◽  
Cell Cell

ανβ3 and α5β1 are essential glycoproteins involved in the pathogenesis of rheumatoid arthritis (RA). Understanding of the role these integrins play in disease have been analyzed via description of cells-expressing ανβ3 and α5β1 and their mediators to trigger inflammation. ανβ3 and α5β1 facilitate cells-ECM and cell-cell communication, producing pro-inflammatory factors. Pro-inflammatory factors are essential for the building of undesirable new blood vessels termed angiogenesis which can further lead to destruction of bones and joints. Despite many attempts to target these glycoproteins, there are still some problems, therefore, there is still interest in understanding the synergistic role these integrins play in the pathogenesis of RA. The purpose of this review is to gain insights into the biological effects of ανβ3 and α5β1 in synovial tissues that are relevant to pathogenesis and therapy of RA.

Joint Destructive Role of Mast Cells in Rheumatoid Arthritis

2020 ◽  
Author(s):  
Kyoung-Woon Kim ◽  
Bo-Mi Kim ◽  
Ji-Yeon Won ◽  
Hong-Ki Min ◽  
Kyung-Ann Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mast Cells ◽  
Therapeutic Option ◽  
Joint Destruction ◽  
Osteoclast Differentiation ◽  
Multinucleated Cells ◽  
Synovial Tissues ◽  
Concentration Levels ◽  
Gene Expression Levels

Abstract Background: We aimed to define the inflammatory and tissue-destructive roles of mast cells in rheumatoid arthritis (RA). Methods: Serum and synovial fluid (SF) concentration levels of tryptase, chymase, and histamine were quantified using ELISA. After activating mast cells using IL-33, the production of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMPs was determined using real-time PCR and ELISA. Osteoclastogenesis was assessed in CD14+ monocytes from peripheral blood and SF, which were cultured with IL-33-activated mast cells, by counting TRAP-positive multinucleated cells. Results: The concentration levels of serum tryptase, chymase, and histamine and SF histamine were higher in patients with RA than in controls. FceR1 and c-kit-positive mast cells were higher in RA synovium than in osteoarthritic (OA) synovium. Stimulation of mast cells by IL-33 increased the number of trypatse+chymase- and tryptase+chymase+ mast cells. IL-33 stimulation also increased the gene expression levels of TNF-a, IL-1b, IL-6, IL-17, RANKL, and MMP-9 in mast cells. Furthermore, IL-33 stimulated human CD14+ monocytes to differentiate into TRAP+ multinucleated osteoclasts. When CD14+ monocytes were co-cultured with mast cells, osteoclast differentiation was increased. Additionally, IL-33-activated mast cells stimulated osteoclast differentiation. The inhibition of intercellular contact between mast cells and monocytes using inserts reduced osteoclast differentiation. Conclusions: Mast cells and their mediators such as tryptase, chymase, and histamine were increased in RA synovial tissues and fluid. Mast cells stimulated osteoclast differentiation in monocytes. The inhibition of mast cells could be a new therapeutic option for reducing joint destruction in RA.

scholarly journals SAT0023 THE ROLE OF ADAM12 UPREGULATED PROLIFERATION OF SYNOVIAL MEMBRANE IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 941.2-942
Author(s):  
M. Watanabe ◽  
K. Nishida ◽  
Y. Nasu ◽  
R. Nakahara ◽  
M. Matsuhashi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Moderate Intensity ◽  
Positive Staining ◽  
Chondrocyte Differentiation ◽  
Chugai Pharmaceutical ◽  
Positive Expression ◽  
Synovial Tissues ◽  
Sat 1

Background:ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of a variety of tumors by degrading ECM and shed precursors, thus promoting cell proliferation, invasion, and metastasis1). Additionally, ADAM12 is involved in chondrocyte differentiation from osteoarthritis (OA) patients by regulation of TGFβ1-induced IGF-1 and RUNX-2 expressions2). However, there is no report on the role of ADAM12 for rheumatoid arthritis (RA).Objectives:To investigate the expression and role of ADAM12 in the synovial tissue of RA.Methods:(1) The expression of ADAM12 in synovial tissues from RA (18 cases), OA (5 cases) and healthy control (HC) (3 cases) was examined by immunohistochemistry. The synovial tissues of HC were obtained during surgery of hemiarthroplasty for bone tumors. Three researchers evaluated the positive cell ratio. The samples were scored according to the percentage of positive staining: 0 points (weak positive, positive expression was less than 5%), 1 point (moderate positive, positive expression was between 5% and 50%) and 2 points (strong positive, positive expression was greater than 50%). In addition, the samples were scored according to the staining intensity: 0 points (weak intensity), 1 point (moderate intensity) and 2 points (high intensity). (2) The cultured synovial fibroblasts obtained from RA patients at the surgery (RASF) were stimulated by TNFα (1, 5, 10 ng/mL), TGFβ1 (1, 5, 10 ng/mL), PDGF-BB (1, 5, 10 ng/mL) and TNFα+TGFβ1+PDGF-BB (all 10 ng/mL), and the expression levels of ADAM12 relative mRNA was examined by real-time PCR. (3) siADAM12 was transfected in RASF, and the proliferation was examined by WST-1 assay, and the expression of ADAM12 protein was examined by western blotting.Results:(1) ADAM12 positive cells were found in synovial lining cells, plasma cells, and vascular endothelial cells. ADAM12 was highly expressed in RA synovial tissues. The immunostaining scores of RA, OA, and HC were 3.9±0.01, 1.9±0.27, and 0.8±0.18, respectively. (2) Stimulation by TNFα, TGFβ1, and PDGF-BB resulted in the upregulation of the expression of ADAM12 relative mRNA in RASF, and TGFβ1 stimulation notably tended to increase the expression by about 5 to 6 times. (3) siADAM12 successfully suppressed the expression of ADAM12 protein and simultaneously suppressed the proliferation of RASF.Conclusion:ADAM12 might be involved in the pathogenesis of RA, promoting the cell proliferation of RASF.References:[1] Kyeiborg M, Albrechtsen R, Couchman J, et al., Cellular roles of ADAM12 in health and disease, Int J Biochem Cell Biol, 2008[2] Masahiro H, Keiichiro N, Joe H, et al., Involvement of ADAM12 in Chondrocyte Differentiation by Regulation of TGF-beta1-Induced IGF-1 and RUNX-2 Expressions, Calcif Tissue Int, 2019Disclosure of Interests:Masahito Watanabe: None declared, Keiichiro Nishida Grant/research support from: K. Nishida has received scholarship donation from CHUGAI PHARMACEUTICAL Co., Eisai Co., Mitsubishi Tanabe Pharma and AbbVie GK., Speakers bureau: K. Nishida has received speaking fees from CHUGAI PHARMACEUTICAL Co., Eli Lilly, Janssen Pharmaceutical K.K., Eisai Co. and AYUMI Pharmaceutical Corporation., Yoshihisa Nasu: None declared, Ryuichi Nakahara: None declared, Minami Matsuhashi: None declared, Yoshifumi Hotta: None declared, Toshifumi Ozaki: None declared

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