ArticleArthritis and rheumatism2013
Loss of methylation in CpG sites in the NF-κB enhancer elements of inducible nitric oxide synthase is responsible for gene induction in human articular chondrocytes.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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59 citing papers in PubMed, 93 citations in OpenAlex.
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- Current understanding of osteoarthritis pathogenesis and relevant new approaches.Bone research · 2022Review
- Natural Compounds Affecting Inflammatory Pathways of Osteoarthritis.Antioxidants (Basel, Switzerland) · 2022Review
- 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
- Assessment of the Efficacy of Bone Marrow-Derived Mesenchymal Stem Cells against a Monoiodoacetate-Induced Osteoarthritis Model in Wistar Rats.Stem cells international · 2022Article
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- Mechanisms of Ataxia Telangiectasia Mutated (ATM) Control in the DNA Damage Response to Oxidative Stress, Epigenetic Regulation, and Persistent Innate Immune Suppression Following Sepsis.Antioxidants (Basel, Switzerland) · 2021Review
- DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review.International journal of molecular sciences · 2021Review
- CpG Site-Specific Regulation of Metallothionein-1 Gene Expression.International journal of molecular sciences · 2020Article
- DNA methylation of noncoding RNAs: new insights into osteogenesis and common bone diseases.Stem cell research & therapy · 2020Review
- DNA hypomethylation during MSC chondrogenesis occurs predominantly at enhancer regions.Scientific reports · 2020Article
- Analysis of methylation datasets identified significantly changed genes and functional pathways in osteoarthritis.Clinical rheumatology · 2019Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveTo investigate whether the abnormal expression of inducible nitric oxide synthase (iNOS) by osteoarthritic (OA) human chondrocytes is associated with changes in the DNA methylation status in the promoter and/or enhancer elements of iNOS.
methodsExpression of iNOS was quantified by quantitative reverse transcriptase-polymerase chain reaction. The DNA methylation status of the iNOS promoter and enhancer regions was determined by bisulfite sequencing or pyrosequencing. The effect of CpG methylation on iNOS promoter and enhancer activities was determined using a CpG-free luciferase vector and a CpG methyltransferase. Cotransfections with expression vectors encoding NF-κB subunits were carried out to analyze iNOS promoter and enhancer activities in response to changes in methylation status.
resultsThe 1,000-bp iNOS promoter has only 7 CpG sites, 6 of which were highly methylated in both control and OA samples. The CpG site at -289 and the sites in the starting coding region were largely unmethylated in both groups. The NF-κB enhancer region at -5.8 kb was significantly demethylated in OA samples compared with control samples. This enhancer element was transactivated by cotransfection with the NF-κB subunit p65, alone or together with p50. Critically, methylation treatment of the iNOS enhancer element significantly decreased its activity in a reporter assay.
conclusionThese findings demonstrate the association between demethylation of specific NF-κB-responsive enhancer elements and the activation of iNOS transactivation in human OA chondrocytes, consistent with the differences in methylation status observed in vivo in normal and human OA cartilage and, importantly, show association with the OA process.
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