scholarly journals Transformation of fibroblast‐like synoviocytes in rheumatoid arthritis; from a friend to foe

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mohammad Javad Mousavi ◽  
Jafar Karami ◽  
Saeed Aslani ◽  
Mohammad Naghi Tahmasebi ◽  
Arash Sharafat Vaziri ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Treatment Strategies ◽  
Oxygen Metabolism ◽  
Systemic Autoimmune Disease ◽  
Epigenetic Alterations ◽  
Pannus Formation ◽  
Type B ◽  
Comprehensive Understanding ◽  
Genetic Abnormalities ◽  
Fibroblast Like Synoviocytes

AbstractSwelling and the progressive destruction of articular cartilage are major characteristics of rheumatoid arthritis (RA), a systemic autoimmune disease that directly affects the synovial joints and often causes severe disability in the affected positions. Recent studies have shown that type B synoviocytes, which are also called fibroblast-like synoviocytes (FLSs), as the most commonly and chiefly resident cells, play a crucial role in early-onset and disease progression by producing various mediators. During the pathogenesis of RA, the FLSs’ phenotype is altered, and represent invasive behavior similar to that observed in tumor conditions. Modified and stressful microenvironment by FLSs leads to the recruitment of other immune cells and, eventually, pannus formation. The origins of this cancerous phenotype stem fundamentally from the significant metabolic changes in glucose, lipids, and oxygen metabolism pathways. Moreover, the genetic abnormalities and epigenetic alterations have recently been implicated in cancer-like behaviors of RA FLSs. In this review, we will focus on the mechanisms underlying the transformation of FLSs to a cancer-like phenotype during RA. A comprehensive understanding of these mechanisms may lead to devising more effective and targeted treatment strategies.

scholarly journals Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

2022 ◽  
Vol 23 (2) ◽  
pp. 905
Author(s):  
Sunhee Jang ◽  
Eui-Jong Kwon ◽  
Jennifer Jooha Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Autoimmune Disease ◽  
Immune Cells ◽  
Cartilage Destruction ◽  
Systemic Autoimmune Disease ◽  
Pannus Formation ◽  
Systemic Complications ◽  
Tissue Proliferation ◽  
Novel Therapeutic

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

TSP1 is the essential domain of SEMA5A involved in pannus formation in rheumatoid arthritis

Rheumatology ◽  
2021 ◽  
Author(s):  
Chipeng Xiao ◽  
Chen Lv ◽  
Siyuan Sun ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transcriptome Sequencing ◽  
Bioinformatics Analysis ◽  
Tube Formation ◽  
Pannus Formation ◽  
Joint Injury ◽  
Formation Experiment ◽  
Essential Domain ◽  
Fibroblast Like Synoviocytes

Abstract Objective In this study, we explored the effect of semaphorin5A (SEMA5A) on rheumatoid arthritis (RA) pathogenesis and its specific TSP1 domain on pannus formation. Methods The expression of SEMA5A was detected in synovium, fibroblast-like synoviocytes (FLS) and synovial fluid of RA patients and healthy controls (HCs) by q-PCR, IHC, WB and ELISA. SEMA5A-mAb intervention was performed to appraise the severity of joints in CIA model. Transcriptome sequencing and bioinformatics analysis in SEMA5A transfected FLS from HCs were performed to screen differentially expressed genes after SEMA5A overexpression. MTT assay in RA-FLS, chicken embryo allantoic membrane experiment and tube formation experiment were used to clarify the influence of SEMA5A on cell proliferation and angiogenesis. Furthermore, rescue experiment verified the function of TSP1 domain of SEMA5A in the progress of RA with Sema5a-/- CIA mice. Results The expression of SEMA5A increased in RA compared with HCs. Simultaneously, SEMA5A-mAb significantly attenuated joint injury and inflammatory response in CIA models. Besides, transcriptome sequencing and angiogenesis-related experiments verified the ability of SEMA5A to promote FLS proliferation and angiogenesis. Moreover, TSP1 was proved as an essential domain in SEMA5A-inducing angiogenesis in vitro. Additionally, rescue of TSP1-deleted SEMA5A failed to deteriorate the severity of arthritis in CIA model constructed with Sema5a -/- mice. Conclusions In summary, up-regulation of SEMA5A was firstly confirmed in pathological lesion of RA patients. Furthermore, the treatment of SEMA5A-mAb attenuated the progress of RA in CIA model. Moreover, TSP1 was indicated as the key domain of SEMA5A to promote pannus formation in RA.

scholarly journals miR-653-5p suppresses the viability and migration of fibroblast-like synoviocytes by targeting FGF2 and inactivation of the Wnt/beta-catenin pathway

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Peilong Dong ◽  
Xiaobo Tang ◽  
Jian Wang ◽  
Botao Zhu ◽  
Zhiyun Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Viability ◽  
Luciferase Reporter ◽  
Systemic Autoimmune Disease ◽  
Beta Catenin ◽  
Protein Levels ◽  
Rho Family ◽  
Synovial Tissues ◽  
And Migration ◽  
Fibroblast Like Synoviocytes

Abstract Background Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Several studies reported that fibroblast-like synoviocytes (FLSs) and miRNAs are associated with RA pathogenesis. This study explored the function of miR-653-5p in the regulation of human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cells. Methods The mRNA and protein levels of genes were measured by RT-qPCR and western blot, respectively. MTT, wound healing, and invasion assays were used to evaluate the viability and metastasis of FLSs. Luciferase reporter and RNA pull-down assays were employed to determine the interaction between miR-653-5p and FGF2. Results RT-qPCR results demonstrated that miR-653-5p expression was decreased and FGF2 level was increased in synovial tissues and FLSs of RA. Moreover, the viability and metastasis of FLSs were accelerated by miR-653-5p addition, which was restrained by miR-653-5p suppression. Furthermore, we demonstrated that levels of Rac1, Cdc42, and RhoA were decreased after miR-653-5p addition. Besides, luciferase reporter and RNA pull-down assays implied that miR-653-5p targeted the 3′-UTR of FGF2. Functional assays showed that FGF2 overexpression neutralized the suppressive effects of miR-653-5p addition on HFLS-RA cell viability, metastasis, and the levels of Rho family proteins. Meanwhile, the levels of β-catenin, cyclin D1, and c-myc were declined by miR-653-5p supplementation, but enhanced by FGF2 addition. Conclusion In sum, we manifested that miR-653-5p restrained HFLS-RA cell viability and metastasis via targeting FGF2 and repressing the Wnt/beta-Catenin pathway.

Ultra Low Field MR Imaging of Cervical Spine Involvement in Rheumatoid Arthritis

1992 ◽  
Vol 33 (2) ◽  
pp. 89-92 ◽  
Author(s):  
M. Fagerlund ◽  
J. Björnebrink ◽  
L. Ekelund ◽  
G. Toolanen
Keyword(s):  
Rheumatoid Arthritis ◽  
Mr Imaging ◽  
Clinical Symptoms ◽  
Treatment Strategies ◽  
Cord Compression ◽  
Craniocervical Junction ◽  
Plain Radiography ◽  
Pannus Formation ◽  
Low Field ◽  
Diagnostic Usefulness

In a study of 30 patients with longstanding rheumatoid arthritis the diagnostic usefulness of ultra low field MR equipment was analyzed in assessing lesions of the craniocervical junction. It was found that at 0.04 T all the examinations were diagnostic and that in combination with plain radiography the diagnostic information obtained was valuable in further planning of the treatment strategies. The neurologic findings were related to the degree and severity of atlantoaxial luxation, either horizontal or vertical, and to the periodontoid pannus formation. The correlation between the degree of cord compression shown with MR imaging and the clinical symptoms, especially long tract symptoms, was poor. The only correlating factor was the duration of the disease.

scholarly journals Epigenetic alterations in rheumatoid arthritis fibroblast-like synoviocytes

Epigenomics ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 479-492 ◽  
Author(s):  
Karen M Doody ◽  
Nunzio Bottini ◽  
Gary S Firestein
Keyword(s):  
Rheumatoid Arthritis ◽  
Epigenetic Alterations ◽  
Fibroblast Like Synoviocytes

scholarly journals SFRP5 Enhances Wnt5a Induced-Inflammation in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Dorra Elhaj Mahmoud ◽  
Wajih Kaabachi ◽  
Nadia Sassi ◽  
Amel Mokhtar ◽  
Myriam Moalla ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Pannus Formation ◽  
Time Points ◽  
Protein Levels ◽  
Inflammatory Molecules ◽  
Fibroblast Like Synoviocytes ◽  
Inflammatory Effect

BackgroundTissue derived fibroblast-like synoviocytes (td-FLS) are key actors in pannus formation and contribute to joint destruction and inflammation during rheumatoid arthritis (RA). Several members of the Wnt family, including Wnt5a, may contribute to RA td-FLS activation and can potentially serve as therapeutic targets.ObjectiveThe present work aimed to investigate the expression of Wnt5a signaling elements in RA td-FLS and their potential precursors (fluid derived (fd) FLS and fibrocytes). We also studied the role of Wnt5a in RA td-FLS pro-inflammatory activity and whether the inhibitor SFRP5 could restore Wnt5a-induced synovial dysfunction in vitro.Materials and MethodsThe levels of Wnt5a, SFRP5, Wnt5a receptors/coreceptors and Wnt5a pro-inflammatory targets were determined in cultured RA td-FLS, fd-FLS and fibrocytes using qPCR under basal conditions. The expression of pro-inflammatory molecules was assessed after RA td-FLS stimulation with Wnt5a and SFRP5 at different time points.ResultsOur data showed that td-FLS, fd-FLS and fibrocytes from patients with RA expressed similar levels of Wnt5a and a set of Wnt5a receptors/coreceptors. We also demonstrated that Wnt5a stimulated the expression of the pro-inflammatory targets, especially IL1β, IL8 and IL6 in RA td-FLS. Wnt5a-induced inflammation was enhanced in the presence of SFRP5. Furthermore, Wnt5a alone and in conjunction with SFRP5 inhibited the gene expression of TCF4 and the protein levels of the canonical coreceptor LRP5.ConclusionWnt5a pro-inflammatory effect is not inhibited but enhanced by SFRP5 in RA td-FLS. This research highlights the importance of carefully evaluating changes in Wnt5a response in the presence of SFRP5.

Treatment with Melittin Induces Apoptosis and Autophagy of Fibroblast-like Synoviocytes in Patients with Rheumatoid Arthritis

2020 ◽  
Vol 21 (8) ◽  
pp. 734-740 ◽  
Author(s):  
Shou-di He ◽  
Ning Tan ◽  
Chen-xia Sun ◽  
Kang-han Liao ◽  
Hui-jun Zhu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Caspase 3 ◽  
Joint Destruction ◽  
Joint Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Caspase 9 ◽  
Inflammatory Processes ◽  
Related Proteins ◽  
Local Stimulation ◽  
Fibroblast Like Synoviocytes

Background: Melittin, the major medicinal component of honeybee venom, exerts antiinflammatory, analgesic, and anti-arthritic effects in patients with Rheumatoid Arthritis (RA). RA is an inflammatory autoimmune joint disease that leads to irreversible joint destruction and functional loss. Fibroblast-Like Synoviocytes (FLS) are dominant, special mesenchymal cells characterized by the structure of the synovial intima, playing a crucial role in both the initiation and progression of RA. Objective: In this study, we evaluated the effects of melittin on the viability and apoptosis of FLS isolated from patients with RA. Methods: Cell viability was determined using CCK-8 assays; apoptosis was evaluated by flow cytometry, and the expression levels of apoptosis-related proteins (caspase-3, caspase-9, BAX, and Bcl-2) were also determined. To explore whether melittin alters inflammatory processes in RA-FLS, IL-1β levels were determined using an enzyme-linked immunosorbent assay (ELISA). Furthermore, we performed GFP-LC3 punctate fluorescence dot assays and western blotting (for LC3, ATG5, p62, and Beclin 1) to assess autophagy in RA-FLS. Results: Our results show that melittin can significantly impair viability, promote apoptosis and autophagy, and inhibit IL-1β secretion in RA-FLS. Conclusion: Melittin may be useful in preventing damage to the joints during accidental local stimulation.

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