ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
PRMT6 Epigenetically Drives Metabolic Switch from Fatty Acid Oxidation toward Glycolysis and Promotes Osteoclast Differentiation During Osteoporosis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed.
- Macrophage metabolic reprogramming via HIF-1α-glycolysis drives osteoblast ferroptosis and bone loss through an IL-6-STAT3-dependent redox axis.Redox report : communications in free radical research · 2026Article
- H3K18la in periodontal ligament fibroblasts regulates immune niches and alveolar bone remodeling under mechanical loads.International journal of oral science · 2026Article
- Glycolysis in bone remodeling: from energy supply to signaling regulation.Molecular biology reports · 2026Review
- EGR2 Facilitates LPS-Elicited Microglial Inflammation and Inflammatory Pain by Transcriptionally Activating MRTO4.Neurochemical research · 2026Article
- Prmt6 Deficiency Drives Osteoblast Senescence Promoting Age-Related Osteoporosis via Epigenetic Remodelling of the H3R2me2a/Sting/Ifitm3 Pathway.Journal of cellular and molecular medicine · 2026Article
- Integration of metabolomics and machine learning algorithm for discovery of early diagnostic biomarkers of osteoporosis.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Prmt6 Deficiency or Inhibition Restores Microglial Homeostasis and Promotes Scar-Limited Repair in Adult Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PRMT6 inhibition or deficiency attenuates diabetic neuropathic pain in male mice and is associated with reduced spinal neuroinflammation, microgliosis, and altered p53-p21 signaling.Journal of neuroinflammation · 2026Article
- HECTD4 in human umbilical cord mesenchymal stem cells-derived exosomes alleviates osteoclast differentiation in osteoporosis progression by suppressing RANK m6A modification via promoting METTL3 ubiquitination.Journal of molecular histology · 2026Article
- SLC2A3-Mediated Lactate Metabolism Promotes Lung Cancer Bone Metastasis by Modulating P53 Lactylation and Immune Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Designed bone-targeting ROS-responsive nanoplatform for precision glycolysis inhibition in postmenopausal osteoporosis.Bioactive materials · 2026Article
- Arginine Methylation Antagonizes TEAD3-Mediated Repression to Promote Osteogenic Differentiation by Disrupting RUNX2-Sequestrating Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nutrients and Metabolites as Signalling Molecules in Osteoclasts.Current osteoporosis reports · 2026Review
- Dysregulation of post-translational modifications in glioma: advances in pathological mechanisms and clinical targeting strategies.Journal of translational medicine · 2026Review
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Schwann cell-derived extracellular vesicles inhibit osteoclastogenesis through the PTEN/AKT axis in peripheral nerve-bone crosstalk.Journal of nanobiotechnology · 2026Article
- Bone Marrow Immunometabolic Remodeling in Osteoporosis: From Systemic Risk Factors to Precision Intervention.International journal of general medicine · 2026Review
- The gut-bone axis: mechanisms through which oleic acid regulates bone metabolism and its potential in preventing and treating osteoporosis.Frontiers in nutrition · 2026Review
- Regulation of osteoclastogenesis and bone resorption by fatty acid metabolism: mechanisms and therapeutic opportunities.Frontiers in endocrinology · 2026Review
- Molecular mechanisms and translational prospects in osteoporosis.Frontiers in endocrinology · 2026Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Epigenetic regulation of metabolism profoundly influences cell fate commitment. During osteoclast differentiation, the activation of RANK signaling is accompanied by metabolic reprogramming, but the epigenetic mechanisms by which RANK signaling induces this reprogramming remain elusive. By transcriptional sequence and ATAC analysis, this study identifies that activation of RANK signaling upregulates PRMT6 by epigenetic modification, triggering a metabolic switching from fatty acids oxidation toward glycolysis. Conversely, Prmt6 deficiency reverses this shift, markedly reducing HIF-1α-mediated glycolysis and enhancing fatty acid oxidation. Consequently, PRMT6 deficiency or inhibitor impedes osteoclast differentiation and alleviates bone loss in ovariectomized (OVX) mice. At the molecular level, Prmt6 deficiency reduces asymmetric dimethylation of H3R2 at the promoters of genes including Ppard, Acox3, and Cpt1a, enhancing genomic accessibility for fatty acid oxidation. PRMT6 thus emerges as a metabolic checkpoint, mediating metabolic switch from fatty acid oxidation to glycolysis, thereby supporting osteoclastogenesis. Unveiling PRMT6's critical role in epigenetically orchestrating metabolic shifts in osteoclastogenesis offers a promising target for anti-resorptive therapy.
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Registered trials
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