ArticleNature medicine2015
DNA methyltransferase 3a regulates osteoclast differentiation by coupling to an S-adenosylmethionine-producing metabolic pathway.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 139 papers, 2 of them syntheses that pooled it.
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Who cites it
139 citing papers in PubMed, 2 syntheses or guidelines pooled it, 221 citations in OpenAlex.
- Regulation of differentiation and generation of osteoclasts in rheumatoid arthritis.Frontiers in immunology · 2022Pooled it
- Interplay Between Glucose Metabolism and Chromatin Modifications in Cancer.Frontiers in cell and developmental biology · 2021Pooled it
- Thromboxane A2 receptor signalling amplifies osteoclastogenesis in rheumatoid arthritis through ACSL1 associated mitochondrial oxidative metabolism.Nature communications · 2026Article
- A Novel Reactive Oxygen Species-Responsive Bone-Targeted Nanoplatform Based on Cloperastine Attenuates Ovariectomy-Induced Bone Loss by Inhibiting Osteoclast Oxidative Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Glucose Metabolic Reprogramming in Exercise-Attenuated Osteoporosis: a Narrative Review.Sports medicine - open · 2026Review
- OXR1 is a dual redox-mitochondrial checkpoint governing osteoclast differentiation and bone loss in an osteoporosis mouse model.Nature communications · 2026Article
- Methionine restriction and mimetics to ameliorate human aging and disease.Trends in endocrinology and metabolism: TEM · 2026Review
- Hells protects mitochondrial integrity via Nr2f2 suppression during osteoclast differentiation.Cell communication and signaling : CCS · 2026Article
- Hybrid extracellular vesicles drive irreversible mitochondria damage and TCA metabolite deficiency-related chondrocyte senescence.Innovation (Cambridge (Mass.)) · 2026Article
- The metabolites for muscle and osteoclast activity are indicators of femoral neck osteoporosis.Scientific reports · 2026Article
- Nutrients and Metabolites as Signalling Molecules in Osteoclasts.Current osteoporosis reports · 2026Review
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- From molecular mechanisms to translational applications: a parallel assessment of green and black tea modulation of oxidative stress.Nutrition & metabolism · 2025Review
- Dnmt3a-mediated DNA Methylation Regulates P. gingivalis-suppressed Cementoblast Mineralization Partially Via Mitochondria-dependent Apoptosis Pathway.Inflammation · 2025Article
- Chondrocyte fatty acid oxidation drives osteoarthritis via SOX9 degradation and epigenetic regulation.Nature communications · 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
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Human dental follicle stem cell-derived exosomes reduce root resorption by inhibiting periodontal ligament cell pyroptosis.Stem cell research & therapy · 2025Article
- Tumor-derived exosomal lncRNA-MIR193BHG promotes bone metastasis of breast cancer by targeting the miR-489-3p/DNMT3A signaling axis in osteoclasts.Journal of translational medicine · 2025Article
- Tissue-specific roles of de novo DNA methyltransferases.Epigenetics & chromatin · 2025Review
79 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metabolic reprogramming occurs in response to the cellular environment to mediate differentiation, but the fundamental mechanisms linking metabolic processes to differentiation programs remain to be elucidated. During osteoclast differentiation, a shift toward more oxidative metabolic processes occurs. In this study we identified the de novo DNA methyltransferase 3a (Dnmt3a) as a transcription factor that couples these metabolic changes to osteoclast differentiation. We also found that receptor activator of nuclear factor-κB ligand (RANKL), an essential cytokine for osteoclastogenesis, induces this metabolic shift towards oxidative metabolism, which is accompanied by an increase in S-adenosylmethionine (SAM) production. We found that SAM-mediated DNA methylation by Dnmt3a regulates osteoclastogenesis via epigenetic repression of anti-osteoclastogenic genes. The importance of Dnmt3a in bone homeostasis was underscored by the observations that Dnmt3a-deficient osteoclast precursor cells do not differentiate efficiently into osteoclasts and that mice with an osteoclast-specific deficiency in Dnmt3a have elevated bone mass due to a smaller number of osteoclasts. Furthermore, inhibition of DNA methylation by theaflavin-3,3'-digallate abrogated bone loss in models of osteoporosis. Thus, this study reveals the role of epigenetic processes in the regulation of cellular metabolism and differentiation, which may provide the molecular basis for a new therapeutic strategy for a variety of bone disorders.
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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.