ArticleArthritis & rheumatology (Hoboken, N.J.)2014
Association of reduced type IX collagen gene expression in human osteoarthritic chondrocytes with epigenetic silencing by DNA hypermethylation.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
58 citing papers in PubMed, 87 citations in OpenAlex.
- The common pathological network of inflammation, extracellular matrix imbalance, and senescence in intervertebral disc degeneration and osteoarthritis.Molecular biology reports · 2026Review
- seneR: An R package for comprehensive senescence assessment and its application in type 2 diabetes and osteoarthritis.Computational and structural biotechnology journal · 2026Article
- Exploring senescence markers as potential drivers of osteoarthritis pain in aging adults.Experimental gerontology · 2025Review
- 3-D biomechanics and epigenomics reveal atypical fibroblast responses in cardiometabolic disease.American journal of physiology. Heart and circulatory physiology · 2025Article
- KMT2D/ZNF460-induced COL9A1-mediated extracellular matrix stiffness maintains the cancer stem cell pool to promote colorectal cancer progression.Cell biology and toxicology · 2025Article
- SOX9: a novel janus-faced regulator in immunity and its promise as a therapeutic target.Frontiers in molecular biosciences · 2025Review
- Spatiotemperal Dynamics of Osteoarthritis: Bridging Insights from Bench to Bedside.Aging and disease · 2024Review
- Review
- Nutritional Epigenomics: Bioactive Dietary Compounds in the Epigenetic Regulation of Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- A Novel BD2-Selective Inhibitor of BRDs Mitigates ROS Production and OA Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Article
- Data-driven identification of predictive risk biomarkers for subgroups of osteoarthritis using interpretable machine learning.Nature communications · 2024Article
- The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis.International journal of molecular sciences · 2023Review
- Epigenetics as a Therapeutic Target in Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Regulatory role of NFAT1 signaling in articular chondrocyte activities and osteoarthritis pathogenesis.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2023Article
- Role of epigenetics and the transcription factor Sp1 in the expression of the D prostanoid receptor 1 in human cartilage.Frontiers in cell and developmental biology · 2023Article
- The identification of hub-methylated differentially expressed genes in osteoarthritis patients is based on epigenomic and transcriptomic data.Frontiers in medicine · 2023Article
- The epigenetic players and the chromatin marks involved in the articular cartilage during osteoarthritis.Frontiers in physiology · 2023Review
- Trichostatin A-Mediated Epigenetic Modulation Predominantly Triggers Transcriptomic Alterations in the Ex Vivo Expanded Equine Chondrocytes.International journal of molecular sciences · 2022Article
- Epigenetic Regulation of Chondrocytes and Subchondral Bone in Osteoarthritis.Life (Basel, Switzerland) · 2022Review
- Histone Extraction from Human Articular Cartilage for the Study of Epigenetic Regulation in Osteoarthritis.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
objectiveTo investigate whether the changes in collagen gene expression in osteoarthritic (OA) human chondrocytes are associated with changes in the DNA methylation status in the COL2A1 enhancer and COL9A1 promoter.
methodsExpression levels were determined using quantitative reverse transcription-polymerase chain reaction, and the percentage of DNA methylation was quantified by pyrosequencing. The effect of CpG methylation on COL9A1 promoter activity was determined using a CpG-free vector; cotransfections with expression vectors encoding SOX9, hypoxia-inducible factor 1α (HIF-1α), and HIF-2α were carried out to analyze COL9A1 promoter activities in response to changes in the methylation status. Chromatin immunoprecipitation assays were carried out to validate SOX9 binding to the COL9A1 promoter and the influence of DNA methylation.
resultsAlthough COL2A1 messenger RNA (mRNA) levels in OA chondrocytes were 19-fold higher than those in the controls, all of the CpG sites in the COL2A1 enhancer were totally demethylated in both samples. The levels of COL9A1 mRNA in OA chondrocytes were 6,000-fold lower than those in controls; 6 CpG sites of the COL9A1 promoter were significantly hypermethylated in OA patients as compared with controls. Treatment with 5-azadeoxycitidine enhanced COL9A1 gene expression and prevented culture-induced hypermethylation. In vitro methylation decreased COL9A1 promoter activity. Mutations in the 5 CpG sites proximal to the transcription start site decreased COL9A1 promoter activity. Cotransfection with SOX9 enhanced COL9A1 promoter activity; CpG methylation attenuated SOX9 binding to the COL9A1 promoter.
conclusionThis first demonstration that hypermethylation is associated with down-regulation of COL9A1 expression in OA cartilage highlights the pivotal role of epigenetics in OA, involving not only hypomethylation, but also hypermethylation, with important therapeutic implications for OA treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.