Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

Zhao, Jianan; Guo, Shicheng; Schrodi, Steven J.; He, Dongyi

doi:10.3389/fimmu.2021.790122

Cited by 79 publications

(69 citation statements)

References 230 publications

(243 reference statements)

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“…Thus, MH7A cells were only used as a reference in drug screening. Numerous chemokines are predicted to contribute to arthritis development because of their high expression levels in the synovial fluid of RA patients or in the arthritic paw of animal models [ 27 ]. Hence, the LPS-induced macrophages, TNF- α -stimulated RASFs, and MH7A cells were used in this study to mimic the inflammation and arthritis models.…”

Section: Discussionmentioning

confidence: 99%

Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling

Chen

Tian

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Objective. This study assessed the anti-arthritic effect and protection of Gedunin (GDN) on joint tissues and revealed the possible mechanism in suppressing rheumatoid arthritis (RA). Methods. LPS-induced macrophages and TNF-α-stimulated synovial fibroblasts (MH7A) or IL-1β-stimulated primary rheumatoid arthritis synovial fibroblasts (RASFs) were used to evaluate the antiinflammatory effect of GDN. In addition, CIA-induced arthritis was employed here to evaluate the anti-arthritic effect. MTT and BRDU assays were utilized to evaluate the cell viability and proliferation, Q-PCR was conducted to detect the mRNA expression of cytokines, FACS was adopted to monitor ROS production, while western blotting (WB) and siRNA interference were applied in confirming the anti-arthritic effects of GDN via the Nrf2 signaling. Results. In vitro, cell viability was inhibited in macrophages and MH7A cells, but not in RASFs; but the proliferation of RASFs was significantly suppressed in time- and dose-dependent manners. GDN suppressed cytokine levels in LPS-stimulated macrophages and TNF-α-stimulated MH7A cells or RASFs. GDN suppressed ROS expression. Furthermore, GDN treatment notably dose-dependently decreased the mRNA and protein expression of iNOS in LPS-induced macrophages. sip62 interference results showed that GDN cause the less expression of HO-1 and Keap1 and also fail to inhibit cytokines after sip62 interference. In vivo, GDN effectively inhibited paw swelling, arthritis score, and arthritis incidence and cytokines. Conclusions. Our study suggested that GDN exhibited strong antagonistic effect on arthritis both in vitro and in vivo via activation of Nrf2 signaling. Our work will provide a promising therapeutic strategy for RA.

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Section: Discussionmentioning

confidence: 99%

Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling

Chen

Tian

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Standard treatment regimens can no longer meet the requirements of individuals for the effectiveness of RA treatment, and known pathogenesis leads researchers to explore more accurate individualized treatment options ( 89 ), although not all of these efforts have positive results. For example, Smith et al.…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Biomarkers to Predict DMARDs Efficacy and Adverse Effect in Rheumatoid Arthritis

et al. 2022

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Rheumatoid arthritis (RA), one of the most common immune system diseases, mainly affects middle-aged and elderly individuals and has a serious impact on the quality of life of patients. Pain and disability caused by RA are significant symptoms negatively affecting patients, and they are especially seen when inappropriate treatment is administered. Effective therapeutic strategies have evolved over the past few decades, with many new disease-modifying antirheumatic drugs (DMARDs) being used in the clinic. Owing to the breakthrough in the treatment of RA, the symptoms of patients who could not be treated effectively in the past few years have been relieved. However, some patients complain about symptoms that have not been reported, implying that there are still some limitations in the RA treatment and evaluation system. In recent years, biomarkers, an effective means of diagnosing and evaluating the condition of patients with RA, have gradually been used in clinical practice to evaluate the therapeutic effect of RA, which is constantly being improved for accurate application of treatment in patients with RA. In this article, we summarize a series of biomarkers that may be helpful in evaluating the therapeutic effect and improving the efficiency of clinical treatment for RA. These efforts may also encourage researchers to devote more time and resources to the study and application of biomarkers, resulting in a new evaluation system that will reduce the inappropriate use of DMARDs, as well as patients’ physical pain and financial burden.

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“…T cells have cellular heterogeneity and can differentiate into different subsets under stimulation by different cytokines, such as Treg cells, Th1 cells, Th2 cells, Th17 cells, and T-follicular helper (Tfh) cells, which play different roles in RA ( 76 ). Th1 and Th17 cell subsets contribute to inflammation in RA.…”

Section: The Effect Of Dna Methylation On the Differentiation Of Cd4+...mentioning

confidence: 99%

DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology

et al. 2022

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Rheumatoid arthritis (RA) is an autoimmune disease that can cause joint damage and disability. Epigenetic variation, especially DNA methylation, has been shown to be involved in almost all the stages of the pathology of RA, from autoantibody production to various self-effector T cells and the defects of protective T cells that can lead to chronic inflammation and erosion of bones and joints. Given the critical role of T cells in the pathology of RA, the regulatory functions of DNA methylation in T cell biology remain unclear. In this review, we elaborate on the relationship between RA pathogenesis and DNA methylation in the context of different T cell populations. We summarize the relevant methylation events in T cell development, differentiation, and T cell-related genes in disease prediction and drug efficacy. Understanding the epigenetic regulation of T cells has the potential to profoundly translate preclinical results into clinical practice and provide a framework for the development of novel, individualized RA therapeutics.

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Molecular and Cellular Heterogeneity in Rheumatoid Arthritis: Mechanisms and Clinical Implications

Cited by 79 publications

References 230 publications

Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling

Importance of Gedunin in Antagonizing Rheumatoid Arthritis via Activating the Nrf2/ARE Signaling

Biomarkers to Predict DMARDs Efficacy and Adverse Effect in Rheumatoid Arthritis

DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology

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