ArticleThe Journal of biological chemistry2013
Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 144 citations in OpenAlex.
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- Epigenetic regulation of inflammation by dopamine in primary human macrophages.Frontiers in immunology · 2026Article
- Expression characteristics of miR-502-5p/p53/NF-κB signaling pathway in patients with different degrees of knee osteoarthritis: a cross-sectional observational study with methodological limitations.Journal of orthopaedic surgery and research · 2025Observational
- Nutritional Epigenomics: Bioactive Dietary Compounds in the Epigenetic Regulation of Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Epigenetic regulation of 15-lipoxygenase-1 expression in human chondrocytes by promoter methylation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
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- Association between DNA Methylation in the Core Promoter Region of the CUT-like Homeobox 1 (Genes · 2023Article
- The epigenetic players and the chromatin marks involved in the articular cartilage during osteoarthritis.Frontiers in physiology · 2023Review
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- Epigenetic Regulation of Chondrocytes and Subchondral Bone in Osteoarthritis.Life (Basel, Switzerland) · 2022Review
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- Apoptosis-associated speck-like protein containing a CARD-mediated release of matrix metalloproteinase 10 stimulates a change in microglia phenotype.Frontiers in molecular neuroscience · 2022Article
- GSK3B Overexpression Alleviates Posttraumatic Osteoarthritis in Mice by Promoting DNMT1-Mediated Hypermethylation of NR4A3 Promoter.Disease markers · 2022Article
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- Analysis of Il36a induction by C/EBPβ via a half-CRE•C/EBP element in murine macrophages in dependence of its CpG methylation level.Genes and immunity · 2021Article
- Transcriptomic and epigenomic analyses uncovered Lrrc15 as a contributing factor to cartilage damage in osteoarthritis.Scientific reports · 2021Article
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- MicroRNA-486 promotes a more catabolic phenotype in chondrocyte-like cells by targeting SIRT6 : possible involvement in cartilage degradation in osteoarthritis.Bone & joint research · 2021Article
29 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 4 countries.
Funding
Abstract
The role of DNA methylation in the regulation of catabolic genes such as MMP13 and IL1B, which have sparse CpG islands, is poorly understood in the context of musculoskeletal diseases. We report that demethylation of specific CpG sites at -110 bp and -299 bp of the proximal MMP13 and IL1B promoters, respectively, detected by in situ methylation analysis of chondrocytes obtained directly from human cartilage, strongly correlated with higher levels of gene expression. The methylation status of these sites had a significant impact on promoter activities in chondrocytes, as revealed in transfection experiments with site-directed CpG mutants in a CpG-free luciferase reporter. Methylation of the -110 and -299 CpG sites, which reside within a hypoxia-inducible factor (HIF) consensus motif in the respective MMP13 and IL1B promoters, produced the most marked suppression of their transcriptional activities. Methylation of the -110 bp CpG site in the MMP13 promoter inhibited its HIF-2α-driven transactivation and decreased HIF-2α binding to the MMP13 proximal promoter in chromatin immunoprecipitation assays. In contrast to HIF-2α, MMP13 transcriptional regulation by other positive (RUNX2, AP-1, ELF3) and negative (Sp1, GATA1, and USF1) factors was not affected by methylation status. However, unlike the MMP13 promoter, IL1B was not susceptible to HIF-2α transactivation, indicating that the -299 CpG site in the IL1B promoter must interact with other transcription factors to modulate IL1B transcriptional activity. Taken together, our data reveal that the methylation of different CpG sites in the proximal promoters of the human MMP13 and IL1B genes modulates their transcription by distinct mechanisms.
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