ArticleArthritis research & therapy2012
Regulation of inflammatory arthritis by the upstream kinase mitogen activated protein kinase kinase 7 in the c-Jun N-terminal kinase pathway.
Article in Arthritis research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Targeting the JNK Gatekeepers: Structural Evolution and Medicinal Chemistry of MKK4 and MKK7 Inhibitors.Molecules (Basel, Switzerland) · 2026Review
- The HRAS-binding C2 domain of PLCη2 suppresses tumor-like synoviocytes and experimental arthritis in rheumatoid arthritis.Experimental & molecular medicine · 2025Article
- Article
- Mitogen-activated protein kinase kinase 7 in inflammatory, cancer, and neurological diseases.Frontiers in cell and developmental biology · 2022Review
- Destructive Roles of Fibroblast-like Synoviocytes in Chronic Inflammation and Joint Damage in Rheumatoid Arthritis.Inflammation · 2021Review
- Article
- Reduction of Articular and Systemic Inflammation by Kava-241 in a Porphyromonas gingivalis-Induced Arthritis Murine Model.Infection and immunity · 2018Article
- Ontology and Function of Fibroblast-Like and Macrophage-Like Synoviocytes: How Do They Talk to Each Other and Can They Be Targeted for Rheumatoid Arthritis Therapy?Frontiers in immunology · 2018Review
- Suppressive Effects of TSAHC in an Experimental Mouse Model and Fibroblast-Like Synoviocytes of Rheumatoid Arthritis.Inflammation · 2017Article
- Anti-Inflammatory Effects and Joint Protection in Collagen-Induced Arthritis after Treatment with IQ-1S, a Selective c-Jun N-Terminal Kinase Inhibitor.The Journal of pharmacology and experimental therapeutics · 2015Article
- A combined "omics" approach identifies N-Myc interactor as a novel cytokine-induced regulator of IRE1 protein and c-Jun N-terminal kinase in pancreatic beta cells.The Journal of biological chemistry · 2014Article
- Myeloid deletion of SIRT1 aggravates serum transfer arthritis in mice via nuclear factor-κB activation.PloS one · 2014Article
- Anti-citrullinated protein antibodies activated ERK1/2 and JNK mitogen-activated protein kinases via binding to surface-expressed citrullinated GRP78 on mononuclear cells.Journal of clinical immunology · 2013Article
- Review
- Anti-inflammatory therapy in chronic disease: challenges and opportunities.Science (New York, N.Y.) · 2013Review
- Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors.Nature reviews. Rheumatology · 2013Review
- Cellular targeting in autoimmunity.Current allergy and asthma reports · 2012Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
introductionThe c-Jun N-terminal kinase (JNK) is a key regulator of matrix metalloproteinase (MMP) and cytokine production in rheumatoid arthritis (RA) and JNK deficiency markedly protects mice in animal models of arthritis. Cytokine-induced JNK activation is strictly dependent on the mitogen-activated protein kinase kinase 7 (MKK7) in fibroblast-like synoviocytes (FLS). Therefore, we evaluated whether targeting MKK7 using anti-sense oligonucleotides (ASO) would decrease JNK activation and severity in K/BxN serum transfer arthritis.
methodsThree 2'-O-methoxyethyl chimeric ASOs for MKK7 and control ASO were injected intravenously in normal C57BL/6 mice. PBS, control ASO or MKK7 ASO was injected from Day -8 to Day 10 in the passive K/BxN model. Ankle histology was evaluated using a semi-quantitative scoring system. Expression of MKK7 and JNK pathways was evaluated by quantitative PCR and Western blot analysis.
resultsMKK7 ASO decreased MKK7 mRNA and protein levels in ankles by about 40% in normal mice within three days. There was no effect of control ASO on MKK7 expression and MKK7 ASO did not affect MKK3, MKK4 or MKK6. Mice injected with MKK7 ASO had significantly less severe arthritis compared with control ASO (P < 0.01). Histologic evidence of synovial inflammation, bone erosion and cartilage damage was reduced in MKK7 ASO-treated mice (P < 0.01). MKK7 deficiency decreased phospho-JNK and phospho-c-Jun in ankle extracts (P < 0.05), but not phospho-MKK4. Interleukin-1beta (IL-1β), MMP3 and MMP13 gene expression in ankle joints were decreased by MKK7 ASO (P < 0.01).
conclusionsMKK7 plays a critical regulatory role in the JNK pathway in a murine model of arthritis. Targeting MKK7 rather than JNK could provide site and event specificity when treating synovitis.
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