ArticleEpigenetics2012
Role of DNA methylation in the regulation of the RANKL-OPG system in human bone.
Article in Epigenetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.Frontiers in immunology · 2022Pooled it
- Epigenome-wide Association of DNA Methylation in Whole Blood With Bone Mineral Density.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017Trial
- Epigenetic Connections in Malocclusion.International journal of molecular sciences · 2026Review
- Diminished osteoprotegerin production by gingival fibroblasts from periodontitis patients is associated with their reduced ability to suppress osteoclastogenesis.Scientific reports · 2025Article
- Integrative Epigenomic and Targeted Protein Analysis in MRONJ: Correlating DNA Methylation with Bone Biomarkers.International journal of molecular sciences · 2025Article
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Inflammatory macrophage-derived itaconate inhibits DNA demethylase TET2 to prevent excessive osteoclast activation in rheumatoid arthritis.Bone research · 2025Article
- Dnmt3a-mediated hypermethylation of FoxO3 promotes redox imbalance during osteoclastogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.Molecular genetics & genomic medicine · 2024Article
- The osteoporosis susceptibility SNP rs188303909 at 2q14.2 regulates EN1 expression by modulating DNA methylation and E2F6 binding.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Comprehensive analysis of epigenetics mechanisms in osteoporosis.Frontiers in genetics · 2023Review
- Topography-mediated immunomodulation in osseointegration; Ally or Enemy.Biomaterials · 2022Review
- Epigenetic regulation of bone mass.Best practice & research. Clinical endocrinology & metabolism · 2022Review
- Genetics and Epigenetics of Bone Remodeling and Metabolic Bone Diseases.International journal of molecular sciences · 2022Review
- The osteocyte as a signaling cell.Physiological reviews · 2022Review
- Genetic Association of rs1021188 and DNA Methylation Signatures ofFrontiers in medicine · 2022Article
- LncRNA SNHG1 modulates adipogenic differentiation of BMSCs by promoting DNMT1 mediated Opg hypermethylation via interacting with PTBP1.Journal of cellular and molecular medicine · 2022Article
- DNA methylation in the OPG/RANK/RANKL pathway is associated with steroid-induced osteonecrosis of the femoral head.BMC musculoskeletal disorders · 2021Article
- DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review.International journal of molecular sciences · 2021Review
- OPG/RANKL/RANK gene methylation among alcohol-induced femoral head necrosis in northern Chinese men.Journal of orthopaedic surgery and research · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoblasts are specialized cells that form new bone and also indirectly influence bone resorption by producing factors that modulate osteoclast differentiation. Although the methylation of CpG islands plays an important role in the regulation of gene expression, there is still scanty information about its role in human bone. The aim of this study was to investigate the influence of CpG methylation on the transcriptional levels of two osteoblast-derived critical factors in the regulation of osteoclastogenesis: the receptor activator of nuclear factor NF-κB ligand (RANKL) and its soluble decoy receptor osteoprotegerin (OPG). Quantitative methylation specific PCR (qMSP) and pyrosequencing analysis in various cell types showed that the methylation of regulatory regions of these genes, in the vicinity of the transcription start sites, repressed gene transcription, whereas an active transcription was associated with low levels of methylation. In addition, treatment with the DNA demethylating agent 5-azadeoxycitidine promoted a 170-fold induction of RANKL and a 20-fold induction of OPG mRNA expression in HEK-293 cells, which showed hypermethylation of the CpG islands and barely expressed RANKL and OPG transcripts at baseline. Transcriptional levels of both genes were also explored in bone tissue samples from patients with hip fractures and hip osteoarthritis. Although RANKL transcript abundance and the RANKL:OPG transcript ratio were significantly higher in patients with fractures than in those with osteoarthritis (RANKL: 0.76 ± 0.23 vs. 0.24 ± 0.08, p = 0.012; RANKL/OPG: 7.66 ± 2.49 vs. 0.92 ± 0.21, p = 0.002), there was no evidence for differential methylation across patient groups. In conclusion, the association between DNA methylation and the repression of RANKL and OPG expression strongly suggests that methylation-dependent mechanisms influence the transcription of these genes, which play a critical role in osteoclastogenesis. However, other mechanisms appear to be involved in the increased RANKL/OPG ratio of patients with osteoporotic fractures.
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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.