ArticleArthritis research & therapy2019
Inhibition of hexokinases holds potential as treatment strategy for rheumatoid arthritis.
Article in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 66 citations in OpenAlex.
- Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.Cellular & molecular immunology · 2026Review
- Machine Learning Analysis of Cytotoxicity Determinants in Nanoparticle-Based Rheumatoid Arthritis Therapies.Molecular pharmaceutics · 2025Article
- Anti-cancer efficacy of novel lonidamine derivatives: Design, synthesis, in vitro, in vivo, and computational studies targeting hexokinase-2.European journal of medicinal chemistry · 2025Article
- Article
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
- Fibroblasts in immune responses, inflammatory diseases and therapeutic implications.Nature reviews. Rheumatology · 2025Review
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- Synergistic metabolic modulation of fibroblast-like synoviocytesActa pharmaceutica Sinica. B · 2025Article
- Hexokinase 2 Suppression Alleviates the Catabolic Properties in Osteoarthritis via HMGA2 and Contributes to Pulsed Electromagnetic Field-mediated Cartilage Protection.International journal of biological sciences · 2025Article
- Integrative multi-omics analyses identify PKD1 and SLC2A4 as genetically supported glycolysis-related candidate genes for rheumatoid arthritis.Frontiers in immunology · 2025Article
- Glucocorticoid receptors involved in ginsenoside compound K ameliorate adjuvant arthritis by inhibiting the glycolysis of fibroblast-like synoviocytes via the NF-κB/HIF-1α pathway.Pharmaceutical biology · 2023Article
- Targeting glycolytic pathway in fibroblast-like synoviocytes for rheumatoid arthritis therapy: challenges and opportunities.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Potential biomarker for diagnosis and therapy of sepsis: Lactylation.Immunity, inflammation and disease · 2023Review
- Hexokinase 2-mediated glycolysis supports inflammatory responses to Porphyromonas gingivalis in gingival fibroblasts.BMC oral health · 2023Article
- Glucose metabolic reprogramming in autoimmune diseases.Animal cells and systems · 2023Review
- The Involvement of Glucose and Lipid Metabolism Alteration in Rheumatoid Arthritis and Its Clinical Implication.Journal of inflammation research · 2023Review
- Macrophage: Key player in the pathogenesis of autoimmune diseases.Frontiers in immunology · 2023Review
- Directly targeting ASC by lonidamine alleviates inflammasome-driven diseases.Journal of neuroinflammation · 2022Article
- miR-124-3p sabotages lncRNA MALAT1 stability to repress chondrocyte pyroptosis and relieve cartilage injury in osteoarthritis.Journal of orthopaedic surgery and research · 2022Article
- Inflammation-Driven Secretion Potential Is Upregulated in Osteoarthritic Fibroblast-Like Synoviocytes.International journal of molecular sciences · 2022Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
introductionAbnormal glycolytic metabolism contributes to joint inflammation and destruction in rheumatoid arthritis (RA). We examine the expression and function of hexokinases in RA and evaluate the potential of their specific inhibitor for clinical treatment.
methodsDetection of HKs was assessed in synovial tissue by immunohistology and Western blot. SiRNA and a specific hexokinases inhibitor, lonidamine (LND), were used to evaluate the role of hexokinase-I/II (HK-I/II). Pro-inflammatory and glycolysis factors, cell viability, and apoptosis were assessed by ELISA, RT-qPCR, MTS, and flow cytometry. The clinical effects of LND on type II collagen-induced arthritis (CIA) in DBA-/1 mouse model was evaluated by scoring their clinical responses, synovitis, and cartilage destructions, and ELISA was employed to analyze the concentrations of antibody in the serum of CIA model.
resultsHK-I/II expression and their activities increased in the synovium of RA compared with osteoarthritis (OA). Silencing HK-I/II (siHK-I/II) or LND treatment decreased the production of pro-inflammatory factors, such as IL-6, IL-8, CXCL9, CXCL10, and CXCL11, and cell viability, but induced cell apoptosis of RASFs. The expression of TNF-α and IL-1β of macrophage in response to LPS stimulation were depressed as well after treatment with siHK-I/II or LND. Furthermore, leucocyte infiltration co-cultured with RASFs was also suppressed after inhibiting the expression or activity of HK-I/II. These anti-inflammatory effects overlapped with their anti-glycolytic activities. Treatment with LND in mice with CIA decreased the production of antibodies against IgG1, IgG2a, and IgG2b and consequently attenuated joint inflammation and destruction.
conclusionsHK-I/II contribute to shape the inflammatory phenotype of RASFs and macrophages. LND may be a potential drug in treating patients with RA.
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