Role of Adiponectin in the Pathogenesis of Rheumatoid Arthritis

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.

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Arthritis and the role of endogenous glucocorticoids

Bone Research ◽

10.1038/s41413-020-00112-2 ◽

2020 ◽

Vol 8 (1) ◽

Cited By ~ 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.

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

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666191210110826 ◽

2020 ◽

Vol 21 (8) ◽

pp. 734-740 ◽

Cited By ~ 1

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

Molecules ◽

10.3390/molecules26164968 ◽

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.

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Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations

Endocrinology ◽

10.1210/en.2007-1312 ◽

2007 ◽

Vol 149 (3) ◽

pp. 1350-1357 ◽

Cited By ~ 94

Author(s):

Florian W. Kiefer ◽

Maximilian Zeyda ◽

Jelena Todoric ◽

Joakim Huber ◽

René Geyeregger ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Plasma Concentrations ◽

Morbidly Obese ◽

Low Grade ◽

Obese Patients ◽

Multifunctional Protein ◽

Inflammatory Processes ◽

Low Grade Inflammation

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.

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The role of YY1 in the pathogenesis of rheumatoid arthritis: A tale of cytokines, ncRNAs, and aberrant fibroblast-like synoviocytes (FLSs)

YY1 in the Control of the Pathogenesis and Drug Resistance of Cancer ◽

10.1016/b978-0-12-821909-6.00018-3 ◽

2021 ◽

pp. 311-335

Author(s):

Yuhao Wang ◽

Benjamin Bonavida

Keyword(s):

Rheumatoid Arthritis ◽

Fibroblast Like Synoviocytes

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Role of cell migration in the pathogenesis of rheumatoid arthritis: in vivo studies in SCID mice transplanted with human synovial membrane

Reumatismo ◽

10.4081/reumatismo.2002.128 ◽

2011 ◽

Vol 54 (2) ◽

Author(s):

F. Ingegnoli ◽

M. Blades ◽

A. Manzo ◽

S. Wahid ◽

M. Perretti ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Cell Migration ◽

Synovial Membrane ◽

Scid Mice ◽

In Vivo Studies

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Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane

J ◽

10.3390/j3020015 ◽

2020 ◽

Vol 3 (2) ◽

pp. 181-194 ◽

Cited By ~ 2

Author(s):

René Huber ◽

Bruno Stuhlmüller ◽

Elke Kunisch ◽

Raimund W. Kinne

Keyword(s):

Rheumatoid Arthritis ◽

Protein Expression ◽

Synovial Membrane ◽

Rna Binding ◽

Mrna Level ◽

Joint Disease ◽

Protein Levels ◽

Modifying Factors ◽

Mrna And Protein Expression ◽

Joint Trauma

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease characterized by overexpression of pro-inflammatory/pro-destructive mediators, whose regulation has been the focus of our previous studies. Since the expression of these proteins commonly depends on AP-1, the expression of the AP-1-forming subunits cJun, JunB, JunD, and cFos was assessed in synovial membrane (SM) samples of RA, osteoarthritis (OA), joint trauma (JT), and normal controls (NC) using ELISA and qRT-PCR. With respect to an observed discrepancy between mRNA and protein levels, the expression of the mRNA stability-modifying factors AU-rich element RNA-binding protein (AUF)-1, tristetraprolin (TTP), and human antigen R (HuR) was measured. JunB and JunD protein expression was significantly higher in RA-SM compared to OA and/or NC. By contrast, jun/fos mRNA expression was significantly (cjun) or numerically decreased (junB, junD, cfos) in RA and OA compared to JT and/or NC. Remarkably, TTP and HuR were also affected by discrepancies between their mRNA and protein levels, since they were significantly decreased at the mRNA level in RA versus NC, but significantly or numerically increased at the protein level when compared to JT and NC. Discrepancies between the mRNA and protein expression for Jun/Fos and TTP/HuR suggest broad alterations of post-transcriptional processes in the RA-SM. In this context, increased levels of mRNA-destabilizing TTP may contribute to the low levels of jun/fos and ttp/hur mRNA, whereas abundant mRNA-stabilizing HuR may augment translation of the remaining mRNA into protein with potential consequences for the composition of the resulting AP-1 complexes and the expression of AP-1-dependent genes in RA.

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The Role of Estrogens in Rheumatoid Arthritis Physiopathology

Rheumatoid Arthritis - Other Perspectives towards a Better Practice ◽

10.5772/intechopen.93371 ◽

2020 ◽

Author(s):

Maria Fernanda Romo-García ◽

Martín Zapata-Zuñiga ◽

José Antonio Enciso-Moreno ◽

Julio Enrique Castañeda-Delgado

Keyword(s):

Rheumatoid Arthritis ◽

Direct Action ◽

Hormone Replacement ◽

Joint Disease ◽

Dependent Manner ◽

Sexual Hormones ◽

Dose Dependent ◽

Estrogen Administration

Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease that can lead to irreversible disability. It affects women in a higher proportion than men (3:1 cases). Several reports suggest a link between female sexual hormones (estrogens) and RA features. It’s been described that biological processes where basal estrogen levels are altered like in menstruation, pregnancy, and menopause modifies RA onset, flare, disease severity, and inflammation. Estrogens have a direct action upon the immune system though ERα and ERβ receptors, which have distinct affinity to estrogen concentrations and modifications and have effects upon RA in a dose and receptor dependent manner. The studies focused on dose dependent response at experimental settings reveal a wide (from 25 pg/L to several μg/L) and even contradictory spectrum of effects in patients and cells. This chapter summarizes the contributions and effects of estrogens in RA physiopathology, clinical features, and discusses the possible contributions of estrogen administration and concentration of hormone replacement therapy (HRT) to improve the quality of life and reduce the symptoms of RA patients based on the knowledge of the biology of these hormones.

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