ArticleThe Journal of experimental medicine2021
Dnmt3a-mutated clonal hematopoiesis promotes osteoporosis.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
103 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis.Blood advances · 2024Pooled it
- Dynamics of clonal hematopoiesis under DNA-damaging treatment in patients with ovarian cancer.Leukemia · 2024Trial
- Efferocytosis activates a DNMT3A-mediated oxidized DNA repair pathway to enable tissue resolution.The Journal of clinical investigation · 2026Article
- Bone health in myelodysplastic neoplasms: results from the prospective longitudinal BoHemE study.Leukemia · 2026Article
- Clinical management of clonal hematopoiesis.Cancer · 2026Review
- Impact of hematologic disorders on decline in hemoglobin levels after total hip arthroplasty.The Journal of international medical research · 2026Article
- Exacerbation of inflammatory bone loss in TET2-driven clonal hematopoiesis.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Hematopoietic mosaic chromosomal alterations are pleiotropic drivers of inflammaging, multimorbidity, and mortality.medRxiv : the preprint server for health sciences · 2026Article
- Macrophage polarization-related genes with potential causal roles in osteoporosis: a multi-omics Mendelian randomization study.Journal of orthopaedic surgery and research · 2026Article
- CHIP clinics: a practical overview of structure and function.Blood cancer journal · 2026Review
- Inflammageing and clonal haematopoiesis interplay and their impact on human disease.Nature reviews. Molecular cell biology · 2026Review
- Clinical decisions in clonal hematopoiesis: a contemporary review for clinicians.Haematologica · 2026Review
- Counting the CHIPs: The High-Stakes Role of Clonal Hematopoiesis in Multiple Myeloma.Biomedicines · 2026Review
- Tet2-driven clonal hematopoiesis drives aortic aneurysm via macrophage-to-osteoclast-like differentiation.The Journal of clinical investigation · 2026Article
- Expanding clones, expanding aneurysms through macrophage-to-osteoclast differentiation.The Journal of clinical investigation · 2026Article
- A prospective study on the regulation of osteoarthritis risk through inflammatory pathways in clonal hematopoiesis.GeroScience · 2026Article
- Review
- Metabolic control of innate immune activation in TET2-mutant clonal hematopoiesis.Cell chemical biology · 2026Article
- Opportunities to Avoid Invasive Cancer by Diagnosis and Interception of Preneoplastic Lesions and Cancer Risk Conditions.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Immune ageing in skeletal fragility: clonal haematopoiesis and failure of inflammatory resolution during fracture repair.Frontiers in immunology · 2026Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
28 authors at 9 institutions in 5 countries.
Funding
Abstract
Osteoporosis is caused by an imbalance of osteoclasts and osteoblasts, occurring in close proximity to hematopoietic cells in the bone marrow. Recurrent somatic mutations that lead to an expanded population of mutant blood cells is termed clonal hematopoiesis of indeterminate potential (CHIP). Analyzing exome sequencing data from the UK Biobank, we found CHIP to be associated with increased incident osteoporosis diagnoses and decreased bone mineral density. In murine models, hematopoietic-specific mutations in Dnmt3a, the most commonly mutated gene in CHIP, decreased bone mass via increased osteoclastogenesis. Dnmt3a-/- demethylation opened chromatin and altered activity of inflammatory transcription factors. Bone loss was driven by proinflammatory cytokines, including Irf3-NF-κB-mediated IL-20 expression from Dnmt3a mutant macrophages. Increased osteoclastogenesis due to the Dnmt3a mutations was ameliorated by alendronate or IL-20 neutralization. These results demonstrate a novel source of osteoporosis-inducing inflammation.
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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.