ArticleMolecular medicine (Cambridge, Mass.)2023
Epigenetic regulatory mechanism of ADAMTS12 expression in osteoarthritis.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Cross-species transcriptome-wide meta-analysis of anterior cruciate ligament rupture.BMC genomics · 2025Pooled it
- PHKG2 confers resistance of ESCC to cisplatin and enhances CXCL8-dependent immunosuppression to exacerbate tumorigenesis.Cell death & disease · 2026Article
- Decorin inhibits the migration and invasion of the LPS + high glucose-induced primary trophoblast cell through ADAMTS12.In vitro cellular & developmental biology. Animal · 2026Article
- METTL3-mCellular & molecular biology letters · 2026Article
- Article
- Microenvironmental response-based treatment of osteoarthritis is a highly effective and durable program: a review.Journal of orthopaedic surgery and research · 2025Review
- Fexofenadine protects against osteoarthritis by targeting Smad2 and STAT1 to enhance anabolism and binding cPLA2 to inhibit catabolism.Cell death discovery · 2025Article
- Circ_0006646 Promotes the Progression of Osteoarthritis via Upregulating CDH11 Expression in an IGF2BP2-Dependent Manner.The Kaohsiung journal of medical sciences · 2025Article
- Cartilage-protective effects of lopinavir/ritonavir: in vitro and in silico exploration of the HIF-1α/SOX9/IL-1β pathway.Journal of orthopaedic surgery and research · 2025Article
- RNA Modifications in Osteoarthritis: Epitranscriptomic Insights into Pathogenesis and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Methyltransferase-Like 3-Mediated NJournal of cellular and molecular medicine · 2025Review
- ADAMTS12 serves as a novel prognostic biomarker and promotes proliferation and invasion in gastric cancer.Discover oncology · 2024Article
- Recent advances of m6A methylation in skeletal system disease.Journal of translational medicine · 2024Review
- Lung Inflammatory Phenotype in Mice Deficient in Fibulin-2 and ADAMTS-12.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOsteoarthritis (OA) is a degenerative joint disease with lacking effective prevention targets. A disintegrin and metalloproteinase with thrombospondin motifs 12 (ADAMTS12) is a member of the ADAMTS family and is upregulated in OA pathologic tissues with no fully understood molecular mechanisms.
methodsThe anterior cruciate ligament transection (ACL-T) method was used to establish rat OA models, and interleukin-1 beta (IL-1β) was administered to induce rat chondrocyte inflammation. Cartilage damage was analyzed via hematoxylin-eosin, Periodic Acid-Schiff, safranin O-fast green, Osteoarthritis Research Society International score, and micro-computed tomography assays. Chondrocyte apoptosis was detected by flow cytometry and TdT dUTP nick-end labeling. Signal transducer and activator of transcription 1 (STAT1), ADAMTS12, and methyltransferase-like 3 (METTL3) levels were detected by immunohistochemistry, quantitative polymerase chain reaction (qPCR), western blot, or immunofluorescence assay. The binding ability was confirmed by chromatin immunoprecipitation-qPCR, electromobility shift assay, dual-luciferase reporter, or RNA immunoprecipitation (RIP) assay. The methylation level of STAT1 was analyzed by MeRIP-qPCR assay. STAT1 stability was investigated by actinomycin D assay.
resultsThe STAT1 and ADAMTS12 expressions were significantly increased in the human and rat samples of cartilage injury, as well as in IL-1β-treated rat chondrocytes. STAT1 is bound to the promoter region of ADAMTS12 to activate its transcription. METTL3/ Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) mediated N6-methyladenosine modification of STAT1 promoted STAT1 mRNA stability, resulting in increased expression. ADAMTS12 expression was reduced and the IL-1β-induced inflammatory chondrocyte injury was attenuated by silencing METTL3. Additionally, knocking down METTL3 in ACL-T-produced OA rats reduced ADAMTS12 expression in their cartilage tissues, thereby alleviating cartilage damage.
conclusionMETTL3/IGF2BP2 axis increases STAT1 stability and expression to promote OA progression by up-regulating ADAMTS12 expression.
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