ArticleMolecular therapy. Methods & clinical development2020
Metformin, an AMPK Activator, Inhibits Activation of FLSs but Promotes HAPLN1 Secretion.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Exploring the therapeutic applications of metformin in articular cartilage repair: mechanistic insights and translational perspectives.Frontiers in immunology · 2026Review
- 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
- HAPLN1 Exhibits Dual Effects: Facilitating Extracellular Matrix Restoration while Enhancing Inflammatory Mediator Production in Arthritic Chondrocytes.Inflammation · 2025Article
- Investigation of the synergistic effect of metformin and FX11 on PANC-1 cell lines.Biological research · 2025Article
- Cardiovascular Risk Factor and Atherosclerosis in Rheumatoid Arthritis (RA).Current cardiology reports · 2025Review
- AMPK signaling in osteoarthritis: from mechanisms to targeted therapeutics.Frontiers in pharmacology · 2025Review
- Mitochondrial metabolic regulation of macrophage polarization in osteomyelitis and other orthopedic disorders: mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Immunomodulatory Effects of SGLT2 Inhibitors and Metformin in Managing Rheumatic Diseases: A Narrative Review.Mediterranean journal of rheumatology · 2024Review
- Medication-related osteonecrosis of the jaw: evolving research for multimodality medical management.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Review
- How Were the Elderly RA Patients Doing Over the Past Year?-A Post Hoc Analysis for Telephone Based Following Up to RA Patients in Zunyi China.Journal of inflammation research · 2024Article
- Jin-Gu-Lian Capsule Did Not Significantly Improve Clinical Value in Rheumatoid Arthritis Therapy: A Real-World Study.Journal of inflammation research · 2024Article
- 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
- Aberrant Activation of Immune and Non-Immune Cells Contributes to Joint Inflammation and Bone Degradation in Rheumatoid Arthritis.International journal of molecular sciences · 2023Review
- Hyaluronan and Proteoglycan Link Protein 1 Activates the BMP4/Smad1/5/8 Signaling Pathway to Promote Osteogenic Differentiation: an Implication in Fracture Healing.Molecular biotechnology · 2023Article
- Metformin Treatment Reduces the Incidence of Rheumatoid Arthritis: A Two-Sample Mendelian Randomized Study.Journal of clinical medicine · 2023Article
- Single-cell analysis reveals heterogeneity of juvenile idiopathic arthritis fibroblast-like synoviocytes with implications for disease subtype.Arthritis research & therapy · 2022Article
- IM156, a new AMPK activator, protects against polymicrobial sepsis.Journal of cellular and molecular medicine · 2022Article
- Cancer-associated fibroblasts-derived HAPLN1 promotes tumour invasion through extracellular matrix remodeling in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- Regulation of Inflammatory Cell Death by Phosphorylation.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AMP-activated protein kinase (AMPK) is essential for maintaining energy balance and has a crucial role in various inflammatory pathways. In this study, AMPK levels positively correlated with many inflammatory indexes in rheumatoid arthritis (RA) patients, especially in the affected synovium. In RA sera, a positive correlation between phosphorylated (p-)AMPK-α1 levels and DAS28 (disease activity score 28) activity (r = 0.270, p < 0.0001) was found. Similarly, a positive correlation was observed between AMPK-α1 and tumor necrosis factor α (TNF-α) levels (r = 0.460, p = 0.0002). Differentially expressed genes between osteoarthritis (OA) and RA synovium from NCBI GEO profiles and our RNA sequencing data suggested activation of metabolic pathways specific to RA-fibroblast-like synoviocytes (FLSs). AMPK-α1 was highly expressed in the synovium of RA but not OA patients. An AMPK activator, metformin, inhibited FLS proliferation at higher but not lower concentrations, whereas the inhibitor dorsomorphin promoted the proliferation of RA-FLSs. Interestingly, both metformin and dorsomorphin inhibited the migration of RA-FLSs. After metformin treatment, expression of interleukin 6 (IL-6), TNF-α, and IL-1β were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-α1, protein kinase A (PKA)-α1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed. Increased levels of HAPLN1 in RA-FLSs by an AMPK activator could potentially be beneficial in protecting the joints. Hence, our results demonstrate the potential of an AMPK activator as a therapeutic for RA.
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