ArticleJournal of orthopaedic surgery and research2020
The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3.
Article in Journal of orthopaedic surgery and research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- IRE1/p‑JNK/NRF2 axis-mediated GPX4 upregulation underlies ferroptosis resistance in rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- A proteomics-based study on the mechanisms of Terminalia chebula Retz processed Aconitum kusnezoffii Reichb against rheumatoid arthritis and its cardiotoxicity reduction.Chinese medicine · 2026Article
- Screening of potential oxidative stress-related biomarkers and therapeutic drugs in rheumatoid arthritis based on integrative bioinformatics, machine learning, and molecular dynamics simulations.Frontiers in molecular biosciences · 2026Article
- Combination of Chenpi and Banxia alleviates synovial inflammation in a rat model of rheumatoid arthritis by targeting the JNK/AP-1 signaling pathway.Frontiers in immunology · 2026Article
- The epigenetic landscape of rheumatoid arthritis: Pathogenesis and drug therapeutic potentials.Acta pharmaceutica Sinica. B · 2025Review
- NF-κB Signaling Pathway in Rheumatoid Arthritis: Mechanisms and Therapeutic Potential.Molecular neurobiology · 2025Review
- Anti-arthritis Effect of Anti-chitinase-3-like 1 Antibody Through Inhibition of MMP3.Immune network · 2025Article
- Precise Control of the in vivo Fate of Nanomicelles Efficiently Treats Advanced Rheumatoid Arthritis via EGFR/JNK/MMP9 Pathway.International journal of nanomedicine · 2025Article
- Rheumatoid Arthritis: Pathogenesis, Therapeutic Strategies, Advances, and Structural Activity Relationships of Synthesized Agents.Current topics in medicinal chemistry · 2025Review
- A Review of Advances in Molecular Imaging of Rheumatoid Arthritis: From In Vitro to Clinic Applications Using Radiolabeled Targeting Vectors with Technetium-99m.Life (Basel, Switzerland) · 2024Review
- Salt Behind the Scenes of Systemic Lupus Erythematosus and Rheumatoid Arthritis.Current nutrition reports · 2023Review
- Rheumatoid Arthritis and Reactive Oxygen Species: A Review.Current issues in molecular biology · 2023Article
- Signaling pathways in rheumatoid arthritis: implications for targeted therapy.Signal transduction and targeted therapy · 2023Review
- N-Acetyl-L-cysteine in human rheumatoid arthritis and its effects on nitric oxide (NO) and malondialdehyde (MDA): analytical and clinical considerations.Amino acids · 2022Review
- Inhibition of Kruppel-like factor 7 attenuates cell proliferation and inflammation of fibroblast-like synoviocytes in rheumatoid arthritis through nuclear factor κB and mitogen-activated protein kinase signaling pathway.Experimental animals · 2022Article
- Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica.Arthritis research & therapy · 2022Article
- Orthodontic force regulates metalloproteinase-3 promoter in osteoblasts and transgenic mouse models.Journal of dental sciences · 2022Article
- Antirheumatoid Arthritic Effects ofFrontiers in pharmacology · 2022Article
- Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis.International journal of molecular sciences · 2021Review
- miR-496/MMP10 Is Involved in the Proliferation of IL-1β-Induced Fibroblast-Like Synoviocytes Via Mediating the NF-κB Signaling Pathway.Inflammation · 2021Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimThe pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management.
methodsWe investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS).
resultsLow-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3.
conclusionsWe demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies.
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