scholarly journals Arthritis and the role of endogenous glucocorticoids

Bone Research ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Eugenie Macfarlane ◽  
Markus J. Seibel ◽  
Hong Zhou
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Current Evidence ◽  
Inflammatory Microenvironment ◽  
Glucocorticoid Signaling ◽  
Anti Inflammatory ◽  
Fibroblast Like Synoviocytes

Abstract Rheumatoid arthritis and osteoarthritis, the most common forms of arthritis, are chronic, painful, and disabling conditions. Although both diseases differ in etiology, they manifest in progressive joint destruction characterized by pathological changes in the articular cartilage, bone, and synovium. While the potent anti-inflammatory properties of therapeutic (i.e., exogenous) glucocorticoids have been heavily researched and are widely used in clinical practice, the role of endogenous glucocorticoids in arthritis susceptibility and disease progression remains poorly understood. Current evidence from mouse models suggests that local endogenous glucocorticoid signaling is upregulated by the pro-inflammatory microenvironment in rheumatoid arthritis and by aging-related mechanisms in osteoarthritis. Furthermore, these models indicate that endogenous glucocorticoid signaling in macrophages, mast cells, and chondrocytes has anti-inflammatory effects, while signaling in fibroblast-like synoviocytes, myocytes, osteoblasts, and osteocytes has pro-inflammatory actions in rheumatoid arthritis. Conversely, in osteoarthritis, endogenous glucocorticoid signaling in both osteoblasts and chondrocytes has destructive actions. Together these studies provide insights into the role of endogenous glucocorticoids in the pathogenesis of both inflammatory and degenerative joint disease.

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.

scholarly journals The Novel Role of MIF in the Secretion of IL-25, IL-31, and IL-33 from PBMC of Patients with Rheumatoid Arthritis

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4968
Author(s):  
Samuel García-Arellano ◽  
Luis Alexis Hernández-Palma ◽  
Sergio Cerpa-Cruz ◽  
Gabriela Athziri Sánchez-Zuno ◽  
Melva Guadalupe Herrera-Godina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Joint Destruction ◽  
Study Groups ◽  
Joint Disease ◽  
The Novel ◽  
Peripheral Blood Mononuclear ◽  
Cytokine Dysregulation ◽  
New Evidence

Rheumatoid arthritis (RA) is an autoimmune inflammatory joint disease with complex pathogenesis associated with cytokine dysregulation. Macrophage migration inhibitory factor (MIF) plays a role in systemic inflammation and joint destruction in RA and could be associated with the secretion of other immune-modulatory cytokines such as IL-25, IL-31, and IL-33. For the above, our main aim was to evaluate the IL-25, IL-31, and IL-33 secretion from recombinant human MIF (rhMIF)-stimulated peripheral blood mononuclear cells (PBMC) of RA patients. The rhMIF and lipopolysaccharide (LPS) plus rhMIF stimuli promote the secretion of IL-25, IL-31, and IL-33 (p < 0.05) from PBMC of RA patients. The study groups, the different stimuli, and the interaction between both showed a statistically significant effect on the secretion of IL-25 (p < 0.05) and IL-31 (p < 0.01). The study of the effect of the RA patient treatments and their interaction with the effect of stimuli did not show an interaction between them. In conclusion, our study generates new evidence for the role of MIF in the secretion of IL-25, IL-31, and IL-33 and its immunomodulatory effect on RA.

scholarly journals Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential Therapeutic Targets

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenggui Miao ◽  
Liangliang Bai ◽  
Yaru Yang ◽  
Jinling Huang
Keyword(s):  
Rheumatoid Arthritis ◽  
Epigenetic Modification ◽  
Joint Destruction ◽  
Research Progress ◽  
Unknown Etiology ◽  
Signal Pathways ◽  
Cartilage Erosion ◽  
Chronic Autoimmune Disease ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology, mainly manifested by persistent abnormal proliferation of fibroblast-like synoviocytes (FLSs), inflammation, synovial hyperplasia and cartilage erosion, accompanied by joint swelling and joint destruction. Abnormal expression or function of long noncoding RNAs (lncRNAs) are closely related to human diseases, including cancers, mental diseases, autoimmune diseases and others. The abnormal sequence and spatial structure of lncRNAs, the disorder expression and the abnormal interaction with the binding protein will lead to the change of gene expression in the way of epigenetic modification. Increasing evidence demonstrated that lncRNAs were involved in the activation of FLSs, which played a key role in the pathogenesis of RA. In this review, the research progress of lncRNAs in the pathogenesis of RA was systematically summarized, including the role of lncRNAs in the diagnosis of RA, the regulatory mechanism of lncRNAs in the pathogenesis of RA, and the intervention role of lncRNAs in the treatment of RA. Furthermore, the activated signal pathways, the role of DNA methylation and other mechanism have also been overview in this review.

scholarly journals The Role of Inflammatory and Anti-Inflammatory Cytokines in the Pathogenesis of Osteoarthritis

2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Piotr Wojdasiewicz ◽  
Łukasz A. Poniatowski ◽  
Dariusz Szukiewicz
Keyword(s):  
Inflammatory Cytokines ◽  
Intracellular Signaling ◽  
Early Stage ◽  
Degenerative Joint Disease ◽  
Antagonistic Effect ◽  
Joint Disease ◽  
Cytokine Network ◽  
Common Chronic Disease ◽  
Anti Inflammatory

Osteoarthritis (OA) is the most common chronic disease of human joints. The basis of pathologic changes involves all the tissues forming the joint; already, at an early stage, it has the nature of inflammation with varying degrees of severity. An analysis of the complex relationships indicates that the processes taking place inside the joint are not merely a set that (seemingly) only includes catabolic effects. Apart from them, anti-inflammatory anabolic processes also occur continually. These phenomena are driven by various mediators, of which the key role is attributed to the interactions within the cytokine network. The most important group controlling the disease seems to be inflammatory cytokines, including IL-1β, TNFα, IL-6, IL-15, IL-17, and IL-18. The second group with antagonistic effect is formed by cytokines known as anti-inflammatory cytokines such as IL-4, IL-10, and IL-13. The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of OA with respect to inter- and intracellular signaling pathways is still under investigation. This paper summarizes the current state of knowledge. The cytokine network in OA is put in the context of cells involved in this degenerative joint disease. The possibilities for further implementation of new therapeutic strategies in OA are also pointed.

scholarly journals Probiotic Supplementation for Rheumatoid Arthritis: A Promising Adjuvant Therapy in the Gut Microbiome Era

2021 ◽  
Vol 12 ◽  
Author(s):  
Margarida Ferro ◽  
Sofia Charneca ◽  
Eduardo Dourado ◽  
Catarina Sousa Guerreiro ◽  
João Eurico Fonseca
Keyword(s):  
Rheumatoid Arthritis ◽  
Adjuvant Therapy ◽  
Functional Disability ◽  
Current Knowledge ◽  
Joint Destruction ◽  
Current Evidence ◽  
Fermented Foods ◽  
Probiotic Supplementation ◽  
Chronic Inflammatory Response

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease that ultimately leads to joint destruction and functional disability. Although the exact etiology of RA is not fully understood, it is well established that gut microbiota (GM) plays a vital role in the pathogenesis of RA, with accumulating evidence suggesting that gut dysbiosis induces a chronic inflammatory response that may be linked to disease development. Of interest, patients with RA have significant changes in the intestinal microbiota compared to healthy controls, and several studies have suggested the use of probiotics as a possible adjuvant therapy for RA. Benefits of probiotic supplementation were reported in animal models of arthritis and human studies, but the current evidence regarding the effect of probiotic supplementation in the management of RA remains insufficient to make definite recommendations. Several different strains of Lactobacillus and Bifidobacteria, as single species or in mixed culture, have been investigated, and some have demonstrated beneficial effects on disease activity in RA human subjects. As of now, L.casei probiotic bacteria seems to be the strongest candidate for application as adjuvant therapy for RA patients. In this review, we highlight the role of GM in the development and progression of RA and summarize the current knowledge on the use of probiotics as a potential adjuvant therapy for RA. We also review the proposed mechanisms whereby probiotics regulate inflammation. Finally, the role of fermented foods is discussed as a possible alternative to probiotic supplements since they have also been reported to have health benefits.

scholarly journals KIAA1199 Biomarker and Ultrasonographic Findings in Rheumatoid Arthritis Patients and their Correlation with Disease Activity

2018 ◽  
Vol 45 (04) ◽  
pp. 341-347
Author(s):  
Zahraa Ibrahim Selim ◽  
Eman H El-Hakeim ◽  
Eman Ahmed Hamed Omran ◽  
Naglaa K. Idriss ◽  
Marwa A. Gaber ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Destruction ◽  
Power Doppler ◽  
Clinical Findings ◽  
Joint Disease ◽  
Knee Joints ◽  
Control Group ◽  
Healthy Control ◽  
Fibroblast Like Synoviocytes

Abstract Introduction Rheumatoid arthritis (RA) is an autoimmune disease that affects multiple joints causing joint destruction. KIAA1199 is a novel angiogenic biomarker derived from fibroblast-like synoviocytes (FLS) it has a role in acceleration and proliferation of FLS and activation of angiogenic signaling pathways leading to erosion of cartilage and bone. Musculoskeletal ultrasound (MUSU) and Power Doppler (PDUS) directly visualizing the synovial membrane vessels, which is important in providing very early information on the changes in synovitis activity during the course of the inflammatory joint disease Objective To assess the serum level of angiogenic biomarker KIAA1199 in RA patients and its correlation with MSUS, PDUS findings, and the disease activity Patients and methods: Fifty RA patients and 40 healthy control persons age and sex-matched were recruited in this study, KIAA1199 was assessed in the serum of patients and controls, MSUS and PDUS were done for the wrist, elbow, and knee joints for all RA patients Results Serum KIAA1199 level was significantly higher among RA patients 4.36±1.22 ng/dl compared to control group 2.87±0.51 ng/dl (p<0.001). There was a highly significant correlation between KIAA1199 level and DAS28 (p=0.004), and there was a significant correlation between the PDUS with KIAA1199 level and DAS28 (p=0.001, 0.002 respectively) in wrist joints Conclusion KIAA1199 is a new pathway that enhancing cell proliferation and angiogenesis. Serum KIAA1199 level may be a useful biomarker for RA activity, and therapeutic target in RA. PDUS correlates significantly with clinical findings and novel angiogenic biomarker in RA patients.

scholarly journals Rheumatoid Arthritis, Depression, and the Role of Celecoxib

2020 ◽  
Vol 2 (10) ◽  
pp. 1848-1852
Author(s):  
Nadeen Al-Baz ◽  
Mustafa Abdul Karim
Keyword(s):  
Rheumatoid Arthritis ◽  
Financial Distress ◽  
Clinical Symptoms ◽  
Joint Destruction ◽  
Modest Improvement ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Chronic Autoimmune Disease ◽  
Biologic Factors

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease, causing joint destruction and associated physical, mental, and financial distress. Depression is not uncommonly found in patients with RA as both disorders share sociodemographic, functional, and biologic factors. There is growing evidence on the role of anti-inflammatory agents in managing depression, particularly celecoxib, which has been shown to significantly alleviate depressive symptoms as an augmenting agent. Compared with traditional nonsteroidal anti-inflammatory drugs (tNSAIDs), however, celecoxib offers modest improvement in clinical symptoms, with uncertain results for pain management, physical function, and adverse effects in patients with RA. Further research is needed to assess the effectiveness of celecoxib in the management of RA, particularly in patients suffering from comorbid depression.

scholarly journals Role of Adiponectin in the Pathogenesis of Rheumatoid Arthritis

2020 ◽  
Vol 21 (21) ◽  
pp. 8265
Author(s):  
Kamila Szumilas ◽  
Paweł Szumilas ◽  
Sylwia Słuczanowska-Głąbowska ◽  
Katarzyna Zgutka ◽  
Andrzej Pawlik
Keyword(s):  
Rheumatoid Arthritis ◽  
Adipose Tissue ◽  
Synovial Membrane ◽  
Joint Disease ◽  
Secretory Product ◽  
Inflammatory Infiltration ◽  
Multifunctional Protein ◽  
Articular Damage ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune joint disease, characterized by progressive articular damage and joint dysfunction. One of the symptoms of this disease is persistent inflammatory infiltration of the synovial membrane, the principle site of inflammation in RA. In the affected conditions, the cells of the synovial membrane, fibroblast-like synoviocytes and macrophage-like synovial cells, produce enzymes degrading cartilage and underlining bone tissue, as well as cytokines increasing the infiltration of immune cells. In patients with RA, higher levels of adiponectin are measured in the serum and synovial fluid. Adiponectin, a secretory product that is mainly white adipose tissue, is a multifunctional protein with dual anti-inflammatory and pro-inflammatory properties. Several studies underline the fact that adiponectin can play an important pro-inflammatory role in the pathophysiology of RA via stimulating the secretion of inflammatory mediators. This narrative review is devoted to the presentation of recent knowledge on the role played by one of the adipokines produced by adipose tissue—adiponectin—in the pathogenesis of rheumatoid arthritis.

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.

scholarly journals The Mechanisms Underlying Chronic Inflammation in Rheumatoid Arthritis from the Perspective of the Epigenetic Landscape

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Yasuto Araki ◽  
Toshihide Mimura
Keyword(s):  
Rheumatoid Arthritis ◽  
Joint Destruction ◽  
Synovial Fibroblasts ◽  
Cell Types ◽  
Epigenetic Mechanisms ◽  
Synovial Hyperplasia ◽  
Genetic And Environmental Factors ◽  
Inflammatory Autoimmune Disease ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is characterized by synovial hyperplasia and progressive joint destruction. The activation of RA synovial fibroblasts (SFs), also called fibroblast-like synoviocytes (FLS), contributes significantly to perpetuation of the disease. Genetic and environmental factors have been reported to be involved in the etiology of RA but are insufficient to explain it. In recent years, accumulating results have shown the potential role of epigenetic mechanisms, including histone modifications, DNA methylation, and microRNAs, in the development of RA. Epigenetic mechanisms regulate chromatin state and gene transcription without any change in DNA sequence, resulting in the alteration of phenotypes in several cell types, especially RASFs. Epigenetic changes possibly provide RASFs with an activated phenotype. In this paper, we review the roles of epigenetic mechanisms relevant for the progression of RA.

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