Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells

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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Diosmetin exhibits anti‐proliferative and anti‐inflammatory effects on TNF‐α‐stimulated human rheumatoid arthritis fibroblast‐like synoviocytes through regulating the Akt and NF‐κB signaling pathways

Phytotherapy Research ◽

10.1002/ptr.6596 ◽

2019 ◽

Vol 34 (6) ◽

pp. 1310-1319 ◽

Cited By ~ 2

Author(s):

You Chen ◽

Yongsheng Wang ◽

Min Liu ◽

Bingkang Zhou ◽

Guangjie Yang

Keyword(s):

Rheumatoid Arthritis ◽

Signaling Pathways ◽

Human Rheumatoid Arthritis ◽

Tnf Α ◽

Anti Inflammatory ◽

Fibroblast Like Synoviocytes

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Rhodojaponin II inhibits TNF‐α‐induced inflammatory cytokine secretion in MH7A human rheumatoid arthritis fibroblast‐like synoviocytes

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22551 ◽

2020 ◽

Vol 34 (10) ◽

Author(s):

Lingli Kong ◽

Laifang Wang ◽

Qing Zhao ◽

Guijuan Di ◽

Huiqiang Wu

Keyword(s):

Rheumatoid Arthritis ◽

Inflammatory Cytokine ◽

Cytokine Secretion ◽

Human Rheumatoid Arthritis ◽

Tnf Α ◽

Fibroblast Like Synoviocytes

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Therapeutic Efficacy of Vitamin Eδ-Tocotrienol in Collagen-Induced Rat Model of Arthritis

BioMed Research International ◽

10.1155/2014/539540 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Nagaraja Haleagrahara ◽

Mirashini Swaminathan ◽

Srikumar Chakravarthi ◽

Ammu Radhakrishnan

Keyword(s):

Rheumatoid Arthritis ◽

Rat Model ◽

Therapeutic Efficacy ◽

Intradermal Injection ◽

Histopathological Analysis ◽

Paw Edema ◽

Collagen Induced Arthritis ◽

Reactive Protein ◽

Significant Reversal ◽

Systemic Inflammatory Disease

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease primarily involving inflammation of the joints. Although the management of the disease has advanced significantly in the past three decades, there is still no cure for RA. The aim of this study was to determine the therapeutic efficacy ofδ-tocotrienol, in the rat model of collagen-induced arthritis (CIA). Arthritis was induced by intradermal injection of collagen type II emulsified in complete Freund’s adjuvant. CIA rats were orally treated withδ-tocotrienol (10 mg/kg) or glucosamine hydrochloride (300 mg/kg) from day 25 to 50. Efficacy was assessed based on the ability to reduce paw edema, histopathological changes, suppression of collagen-specific T-cells, and a reduction in C-reactive protein (CRP) levels. It was established thatδ-tocotrienol had the most significant impact in lowering paw edema when compared to glucosamine treatment. Paw edema changes correlated well with histopathological analysis where there was a significant reversal of changes in groups treated withδ-tocotrienol. The results suggest thatδ-tocotrienol is efficient in amelioration of collagen-induced arthritis. Vitamin E delta-tocotrienol may be of therapeutic value against rheumatoid arthritis.

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Comparative morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

10.21203/rs.3.rs-129415/v1 ◽

2020 ◽

Author(s):

Camilla Machado ◽

Adriana Kakehasi ◽

Felipe Dias ◽

Gustavo Resende ◽

Patrícia Oliveira ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Electron Microscopy ◽

Signaling Pathways ◽

Human Model ◽

Human Rheumatoid Arthritis ◽

Functional Responses ◽

Collagen Induced Arthritis ◽

Ultrastructural Characteristics ◽

Intracellular Pathways ◽

Fibroblast Like Synoviocytes

Abstract BackgroundFibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to compare ultrastructural characteristics and functional responses by human and mouse FLS. The objective of this study is to compare ultrastructural characteristics, IL-6 and MMP-3 production, and the activation of intracellular pathways in FLS from patients with RA (RA-FLS) and mice with collagen-induced arthritis (CIA-FLS). The objective of the study was to compare ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with Rheumatoid Arthritis (RA) and from mice with collagen-induced arthritis.MethodsFLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with collagen-induced arthritis (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor - alpha (TNF-α) and IL-1β.ResultsRA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs.ConclusionThere were differences between RA-FLSs and CIA-FLSs in their ultrastructural morphologies and functional responses. The differences shown in our study indicate that the adoption of an RA-FLS human model is a better alternative than the CIA-FLS animal model for in vitro studies of RA etiopathogenesis and new therapeutic targets.

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The Function and Molecular Mechanism of MicroRNA-429 in Rheumatoid Arthritis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2352 ◽

2020 ◽

Vol 10 (7) ◽

pp. 945-950

Author(s):

Pengdong Zhang ◽

Bailong Yu ◽

Bin Lei ◽

Changlin Li ◽

Xiaoqiang Yuan

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Molecular Mechanism ◽

Synovial Tissue ◽

Luciferase Assay ◽

Rt Pcr ◽

Tnf Α ◽

Tlr4 Gene ◽

Synovial Tissues ◽

D Model

Objective: To explain the function and molecular mechanism of miRNA-429 in Rheumatoid Arthritis development. Methods: Collecting synovial tissue of 36 RA patients and 36 traumatic amputation patients, the miRNA-429 and TLR4 gene expressions were measured by RT-PCR. The SD rats were divided into NC, 14 d Model and 28 d Model groups. The IL-1β and TNF-α concentrations of serum were measured by Elisa assay in difference rats groups; The synovial tissue pathology was evaluated by HE staining; the miRNA-429 gene expression of rats groups were measured by RT-PCR, the TLR4 and NF-κB proteins expressions of rats groups were evaluated by IHC staining; the correlation between miRNA-429 and TLR4 were evaluated by Double luciferase assay. Results: Compared with normal synovial tissues, the miRNA-429 and TLR4 gene expression of synovial tissues were significantly difference in RA patients. In rats vivo study, we found that IL-1 and TNF-α concentrations were significantly up-regulation with time increasing (P < 0 05, respectively); inflammation degree was serious by HE staining and miRNA-429 gene expression was significantly reduced (P < 0.05, respectively); TLR4 and NF-κB proteins expressions were significantly up-regulation (P < 0.05, respectively) with time increasing; TLR4 was the target gene of miRNA-429 by Double luciferase assay. Conclusion: miRNA-429 over-expression stimulated RA development.

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Impact of Schistosoma japonicum Infection on Collagen-Induced Arthritis in DBA/1 Mice: A Murine Model of Human Rheumatoid Arthritis

PLoS ONE ◽

10.1371/journal.pone.0023453 ◽

2011 ◽

Vol 6 (8) ◽

pp. e23453 ◽

Cited By ~ 44

Author(s):

Xiaorong Song ◽

Jilong Shen ◽

Huiqin Wen ◽

Zhengrong Zhong ◽

Qinli Luo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Schistosoma Japonicum ◽

Murine Model ◽

Human Rheumatoid Arthritis ◽

Collagen Induced Arthritis

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Production of anti-CCP antibodies and matrix metalloproteinase-3 by human rheumatoid arthritis synovial tissues using SCID mice

Annals of the Rheumatic Diseases ◽

10.1136/ard.2004.032847 ◽

2005 ◽

Vol 64 (7) ◽

pp. 1094-1095 ◽

Cited By ~ 10

Author(s):

S Iwaki-Egawa

Keyword(s):

Rheumatoid Arthritis ◽

Matrix Metalloproteinase ◽

Scid Mice ◽

Human Rheumatoid Arthritis ◽

Matrix Metalloproteinase 3 ◽

Synovial Tissues

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Down-regulation of microRNA-142-3p inhibits the aggressive phenotypes of rheumatoid arthritis fibroblast-like synoviocytes through inhibiting nuclear factor-κB signaling

Bioscience Reports ◽

10.1042/bsr20190700 ◽

2019 ◽

Vol 39 (7) ◽

Cited By ~ 7

Author(s):

Jianhong Qiang ◽

Tingting Lv ◽

Zhenbiao Wu ◽

Xichao Yang

Keyword(s):

Rheumatoid Arthritis ◽

B Cell Lymphoma ◽

Nuclear Factor Κb ◽

Luciferase Reporter ◽

Nuclear Factor ◽

Down Regulation ◽

Qrt Pcr ◽

Tnf Α ◽

Synovial Tissues ◽

Fibroblast Like Synoviocytes

Abstract The present study aimed to investigate the regulatory roles of miR-142-3p on the aggressive phenotypes of rheumatoid arthritis (RA) human fibroblast-like synoviocytes (RA-HFLSs), and reveal the potential mechanisms relating with nuclear factor-κB (NF-κB) signaling. miR-142-3p expression was detected in RA synovial tissues and RA-HFLSs by quantitative real-time PCR (qRT-PCR) and Northern blot analysis. RA-HFLSs were transfected with miR-142-3p inhibitor and/or treated with 10 µg/l tumor necrosis factor α (TNF-α). The viability, colony formation, apoptosis, migration, invasion, and the levels of interleukin (IL)-6, and matrix metalloproteinase 3 (MMP-3) were detected. The mRNA expressions of B-cell lymphoma-2 (Bcl-2), Bax, Bad, IL-6, and MMP-3 were detected by qRT-PCR. Moreover, the expression of Bcl-2, IL-1 receptor-associated kinase 1 (IRAK1), Toll-like receptor 4 (TLR4), NF-κB p65, and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blot. The interaction between IRAK1 and miR-142-3p was identified by dual luciferase reporter gene assay. MiR-142-3p was up-regulated in RA synovial tissues and RA-HFLSs. TNF-α activated the aggressive phenotypes of RA-HFLSs, including enhanced proliferation, migration, invasion, and inflammation, and inhibited apoptosis. miR-142-3p inhibitor significantly decreased the cell viability, the number of cell clones, the migration rate, the number of invasive cells, the contents and expression of IL-6 and MMP-3, and increased the apoptosis rate and the expressions of Bax and Bad, and decreased Bcl-2 expression of TNF-α-treated RA-HFLSs. MiR-142-3p inhibitor significantly reversed TNF-α-induced up-regulation of IRAK1, TLR4, and p-NF-κB p65 in TNF-α-treated RA-HFLSs. Besides, IRAK1 was a target of miR-142-3p. The down-regulation of miR-142-3p inhibited the aggressive phenotypes of RA-HFLSs through inhibiting NF-κB signaling.

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Ti–O based nanomaterials ameliorate experimental autoimmune encephalomyelitis and collagen-induced arthritis

RSC Advances ◽

10.1039/c5ra18974h ◽

2016 ◽

Vol 6 (11) ◽

pp. 8870-8880 ◽

Cited By ~ 10

Author(s):

T. Sree Latha ◽

Dakshayani Lomada ◽

Praveen Kumar Dharani ◽

Shankar V. Muthukonda ◽

Madhava C. Reddy

Keyword(s):

Rheumatoid Arthritis ◽

Multiple Sclerosis ◽

Experimental Autoimmune Encephalomyelitis ◽

Therapeutic Approach ◽

Clinical Severity ◽

Collagen Induced Arthritis ◽

Autoimmune Encephalomyelitis ◽

Novel Therapeutic ◽

Experimental Autoimmune

Administration of Ti–O based nanomaterials ameliorated the clinical severity of experimental autoimmune encephalomyelitis and collagen induced arthritis, thus provide novel therapeutic approach for multiple sclerosis and rheumatoid arthritis.

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