ArticleBritish journal of pharmacology2017
Inhibition of 6-phosphofructo-2-kinase suppresses fibroblast-like synoviocytes-mediated synovial inflammation and joint destruction in rheumatoid arthritis.
Article in British journal of pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 103 citations in OpenAlex.
- Metabolic-Redox Remodeling of Inflammatory Synovium by Mannose-Modified Selenium Nanoparticles for Osteoarthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- Proteomic Identification of PFKFB3 and PFKFB4 Associated with Coenzyme Metabolism and Redox Imbalance in Dairy Cows with Clinical Mastitis.Antioxidants (Basel, Switzerland) · 2026Article
- Inhibition of PFKFB3 in macrophages ameliorates intestinal inflammation by modulating gut microbiota in DSS-induced colitis.mSystems · 2026Article
- Anti-inflammatory effects of 3PO in asthmatic airway inflammation: an integrated study using network pharmacology, molecular modelling, andFrontiers in pharmacology · 2026Article
- Roles of immune cell metabolism in rheumatoid arthritis.Frontiers in immunology · 2026Review
- Tumor necrosis factor alpha triggers mitochondrial dysfunction and ROS-driven cytokine amplification in bovine fibroblast-like synoviocytes.Frontiers in veterinary science · 2026Article
- Exploring the ubiquitination regulatory network: opening new perspectives for rheumatoid arthritis therapy.Annals of medicine · 2025Review
- Lactylation at the crossroads of immune metabolism and epigenetic regulation: revealing its role in rheumatic immune diseases.Journal of translational medicine · 2025Review
- Histone lactylation promotes rheumatoid arthritis progression by increasing NFATc2 expression and the production of anti-lactylated histone autoantibodies.Nature communications · 2025Article
- PFKFB3-Mediated Glycolytic Metabolic Reprogramming Regulates Inflammatory Response in Dry Eye Disease.Investigative ophthalmology & visual science · 2025Article
- Angiogenesis in rheumatoid Arthritis: Pathological characterization, pathogenic mechanisms, and nano-targeted therapeutic strategies.Bioactive materials · 2025Review
- DDIT4 participates in high glucose-induced fibroblast-like synoviocytes overactivation and cartilage injury by regulating glycolysis.Regenerative therapy · 2025Article
- Novel regulation mechanism of histone methyltransferase SMYD5 in rheumatoid arthritis.Cellular & molecular biology letters · 2025Article
- Synergistic metabolic modulation of fibroblast-like synoviocytesActa pharmaceutica Sinica. B · 2025Article
- Sulfasalazine promotes ferroptosis through AKT-ERK1/2 and P53-SLC7A11 in rheumatoid arthritis.Inflammopharmacology · 2024Article
- Andrographolide Ameliorates Inflammatory Changes Induced by D-Lactate in Bovine Fibroblast-like Synoviocytes.Animals : an open access journal from MDPI · 2024Article
- Implications of siRNA Therapy in Bone Health: Silencing Communicates.Biomedicines · 2024Review
- Noncoding RNAs in rheumatoid arthritis: modulators of the NF-κB signaling pathway and therapeutic implications.Frontiers in immunology · 2024Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAbnormal glycolytic metabolism contributes to joint inflammation in rheumatoid arthritis (RA). The aims of this study were to investigate the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a bifunctional enzyme that controls the glycolytic rate, in regulating fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and invasiveness in RA. EXPERIMENTAL APPROACH: A specific inhibitor of PFKFB3, PFK15, and siRNA were used to evaluate the role of PFKFB3. Protein expression was measured by Western blotting or immunofluorescence staining. The expression of cytokines was determined by quantitative real-time PCR. Migration and invasion were measured using a Boyden chamber assay. A mouse model of collagen-induced arthritis (CIA) was used to evaluate the in vivo effect of PFK15. KEY
resultsPFKFB3 expression was increased in the synovial tissue and FLSs from RA patients compared with osteoarthritis patients. PFKFB3 inhibition decreased the expression of IL-8, IL-6, CCL-2 and CXCL-10 and the proliferation, migration and invasion of RA FLSs. PFK15 suppressed TNF-α-induced activation of NF-κB and p38, JNK and ERK MAPK signals in RA FLSs. PFK15 treatment also suppressed glucose uptake and lactate secretion. Lactate reversed the inhibitory effect of PFK15 or PFKFB3 siRNA on cytokine expression and migration of RA FLSs. Lactate was also involved in PFKFB3-mediated activation of NF-κB and MAPKs. Intraperitoneal injection of PFK15 in mice with CIA attenuated joint inflammation. CONCLUSION AND IMPLICATIONS: Elevated PFKFB3 expression might contribute to synovial inflammation and aggressive behaviours of RA FLSs, suggesting a novel strategy of targeting PFKFB3 to prevent synovial inflammation and joint destruction in RA.
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