ArticleBone research2024
DNMT aberration-incurred GPX4 suppression prompts osteoblast ferroptosis and osteoporosis.
Article in Bone research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of ferroptosis in osteoporosis: a cellular perspective on osteoblast, osteoclast and osteocyte dysfunction.Frontiers in endocrinology · 2026Pooled it
- Quercetin-derived carbon dots-modified ZIF-8 and M2 macrophage-derived migrasomes-functionalized microenvironment-responsive nanocomposite hydrogel for osteoporotic bone defects regeneration.Bioactive materials · 2027Article
- Age-Related Lamin B1 Deficiency Activates SLC7A11-Dependent Disulfidptosis to Impair Osteogenesis via Intercepting Mitochondrial Fission.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Oxidized-Lipid Signaling and Ferroptosis as Downstream Mechanisms of Titanium-Associated Peri-Implant Bone Loss.Antioxidants (Basel, Switzerland) · 2026Review
- Gut Microbiota-Derived Indole-3-Propionic Acid Alleviates Diabetic Osteoporosis Through Nrf2-Mediated Ferroptosis Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cell Type-Specific Ferroptosis Regulatory Networks in the Bone Microenvironment: Implications for the Pathogenesis and Treatment of Osteoporosis.Traffic (Copenhagen, Denmark) · 2026Review
- Gαi1/3 Are Essential for BMP2-Induced Osteogenesis by Bridging BMP Receptors to the Gab1 Signaling Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Valproic Acid Inhibits Ferroptosis and Improves Bone Integration in OVX Rats Through the AMPK/SIRT1 Pathway.The Kaohsiung journal of medical sciences · 2026Article
- Ferroptosis in musculoskeletal disorders: Emerging mechanisms and therapeutic opportunities (Review).International journal of molecular medicine · 2026Review
- BMAL1 Proteostasis, Circadian Dysfunction, and Ferroptotic Vulnerability in Osteoporosis: Current Evidence and Experimental Priorities.Calcified tissue international · 2026Review
- β-Caryophyllene confers protection against type 2 diabetic osteoporosis by blocking ferroptosis via the AMPK/Nrf2 pathway.Journal of pharmaceutical analysis · 2026Article
- Interactions between the gut microbiome and ferroptosis in degenerative diseases: Novel mechanisms and potential therapeutic strategies.Acta pharmaceutica Sinica. B · 2026Review
- Application Strategies of Bone Marrow Mesenchymal Stromal Cells in Bone-Related Diseases.Cell proliferation · 2026Review
- Targeting Ferroptosis With Natural Products for the Treatment of Skeletal System Disease: An Updated Review.Journal of cellular and molecular medicine · 2026Review
- Gαi1/3 Is a Novel Regulatory Target for RANKL Signal Transduction and Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microcystin-LR Triggers Renal Tubular Ferroptosis Through Epigenetic Repression of GPX4: Implications for Environmental Nephrotoxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic and post-translational regulatory networks of ferroptosis in the tumor immune microenvironment.Experimental hematology & oncology · 2026Review
- TET1 as a master regulator controlling GPX4-dependent and -independent ferroptosis surveillance in acute myeloid leukemia.Nature communications · 2026Article
- Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration.Apoptosis : an international journal on programmed cell death · 2026Review
- CRB2 Activates an Epigenetic Axis to Promote Ferroptosis in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Osteoporosis (OP) is a common and fracture-prone skeletal disease characterized by deteriorated trabecular microstructure and pathologically involving various forms of regulated bone cell death. However, the exact role, cellular nature and regulatory mechanisms of ferroptosis in OP are not fully understood. Here, we reported that OP femurs from ovariectomized (Ovx) mice exhibited pronounced iron deposition, ferroptosis, and transcriptional suppression of a key anti-ferroptotic factor GPX4 (glutathione peroxidase 4). GPX4 suppression was accompanied by hypermethylation of the Gpx4 promoter and an increase in DNA methyltransferases DNMT1/3a/3b and was transcriptionally promoted by repressive KLF5 and the transcriptional corepressors NCoR and SnoN. Conversely, DNMT inhibition with SGI-1027 reversed promoter hypermethylation, GPX4 suppression and ferroptotic osteoporosis. In cultured primary bone cells, ferric ammonium citrate (FAC) mimicking iron loading similarly induced GPX4 suppression and ferroptosis in osteoblasts but not in osteoclasts, which were rescued by siRNA-mediated individual knockdown of DNMT 1/3a/3b. Intriguingly, SGI-1027 alleviated the ferroptotic changes caused by FAC, but not by a GPX4 inactivator RSL3. More importantly, we generated a strain of osteoblast-specific Gpx4 haplo-deficient mice Gpx4
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