ArticleAnnals of the rheumatic diseases2016
Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Cuproptosis: New Perspectives for Prevention and Treatment of Osteoarthritis with Chinese Medicine Extracts.Chinese journal of integrative medicine · 2026Review
- Regulated cell death in musculoskeletal development, homeostasis, and diseases.Fundamental research · 2026Review
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Complete Loss of Cramp Promotes Experimental Osteoarthritis with Enhanced Chondrocyte Apoptosis in Mice.International journal of molecular sciences · 2025Article
- The Impact of Selenium Deficiency and T-2 Toxin on Zip6 Expression in Kashin-Beck Disease.Biological trace element research · 2025Article
- Metalloproteins as risk factors for osteoarthritis: improving and understanding causal estimates using Mendelian randomization.Clinical rheumatology · 2024Article
- Annexin A5 Derived from Cell-free Fat Extract Attenuates Osteoarthritis via Macrophage Regulation.International journal of biological sciences · 2024Article
- Article
- Swimming prevents cell death of chondrocytes via PI3K/AKT pathway in an experimental model.Journal of orthopaedic surgery and research · 2023Article
- Monotropein attenuates apoptosis and pyroptosis in chondrocytes and alleviates osteoarthritis progression in mice.Chinese medicine · 2023Article
- Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis.Journal of orthopaedic surgery and research · 2022Article
- Sirtuin 1 participates in intervertebral disc degeneration via the nicotinamide phosphoribosyl transferase/nicotinamide adenine dinucleotide/sirtuin 1 pathway responsible for regulating autophagy of nucleus pulposus cells.Experimental and therapeutic medicine · 2022Article
- Comparison of Gene Expression Patterns in Articular Cartilage and Xiphoid Cartilage.Biochemical genetics · 2022Article
- Inhibitors of Human Divalent Metal Transporters DMT1 (SLC11A2) and ZIP8 (SLC39A8) from a GDB-17 Fragment Library.ChemMedChem · 2021Article
- Inhibitory Effects of IL-6-Mediated Matrix Metalloproteinase-3 and -13 byPharmaceuticals (Basel, Switzerland) · 2021Article
- ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses.Experimental & molecular medicine · 2021Article
- Comparison of Bone Tissue Trace Element Content in the Different Radiological Stages of Hip Osteoarthritis.International journal of environmental research and public health · 2021Article
- Silencing of TLR7 protects against lipopolysaccharide-induced chondrocyte apoptosis and injury by blocking the p21-mediated JAK2/STAT3 pathway.American journal of translational research · 2021Article
- Regulation of gene expression by MF63, a selective inhibitor of microsomal PGE synthase 1 (mPGES1) in human osteoarthritic chondrocytes.British journal of pharmacology · 2020Article
- MiR-155 promotes interleukin-1β-induced chondrocyte apoptosis and catabolic activity by targeting PIK3R1-mediated PI3K/Akt pathway.Journal of cellular and molecular medicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe zinc-ZIP8-MTF1 axis induces metallothionein (MT) expression and is a catabolic regulator of experimental osteoarthritis (OA) in mice. The main aim of the current study was to explore the roles and underlying molecular mechanisms of MTs in OA pathogenesis.
methodsExperimental OA in mice was induced by destabilisation of the medial meniscus or intra-articular injection of adenovirus carrying a target gene (Ad-Zip8, Ad-Mtf1, Ad-Epas1, Ad-Nampt, Ad-Mt1 or Ad-Mt2) into wild type, Zip8
resultsMTs were highly expressed in human and mouse OA cartilage. Hypoxia-inducible factor 2α, nicotinamide phosphoribosyltransferase and several proinflammatory cytokine pathways, as well as the zinc-ZIP8-MTF1 axis were identified as upstream regulators of MT expression. Genetic deletion of Mt1 and Mt2 enhanced cartilage destruction through increasing chondrocyte apoptosis. Unexpectedly, aberrant overexpression of MT2, but not MT1, induced upregulation of matrix-degrading enzymes and downregulation of matrix molecules through nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1) activation, ultimately leading to OA.
conclusionsMTs play an antiapoptotic role in post-traumatic OA. However, aberrant and chronic upregulation of MT2 triggers an imbalance between chondrocyte anabolism and catabolism, consequently accelerating OA development. Our findings collectively highlight pleiotropic roles of MTs as regulators of chondrocyte apoptosis as well as catabolic and anabolic pathways during OA pathogenesis.
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