The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3

Journal of Orthopaedic Surgery and Research
Tomotake KanaiNaoto Endo

Abstract

The 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. We 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...Continue Reading

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Citations

Aug 15, 2020·Frontiers in Pharmacology·Liliya N KirpotinaMark T Quinn
Jul 10, 2021·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Shuang LiuPing Xin

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Methods Mentioned

BETA
Protein Assay
electrophoresis
X-ray

Software Mentioned

GraphPad Prism
ImageJ
Muse Cell Analyzer
GraphPad

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