ArticleAnnals of the rheumatic diseases2023
Neutrophil extracellular trap-associated carbamylation and histones trigger osteoclast formation in rheumatoid arthritis.
Article in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 citations in OpenAlex.
- Mitochondria: a breakthrough in combating rheumatoid arthritis.Frontiers in medicine · 2024Pooled it
- Global research trends and focus on the link between rheumatoid arthritis and neutrophil extracellular traps: a bibliometric analysis from 1985 to 2023.Frontiers in immunology · 2023Pooled it
- Preoperative neutrophil-to-lymphocyte ratio and refracture risk in hip fracture patients: a propensity score-matched analysis.Annals of medicine · 2026Article
- Neutrophils: The Overlooked Regenerative Role in Bone Repair.Stem cell reviews and reports · 2026Review
- Updates on the Evaluation of Lupus Arthritis.Rheumatology and therapy · 2026Review
- Anti-Carbamylated Protein Antibodies Stabilize Carbamylated Histone H3 to Promote Synovial Activation and Neutrophil Extracellular Trap-Mediated Bone Loss in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- NLRX1 is a critical neutrophil checkpoint modulating ferroptosis and suppressing NETosis to attenuate joint damage in arthritis.Cell death and differentiation · 2026Article
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- Spatial proteomics reveals four-stage molecular evolution in cancer immunotherapy-related gastritis.Molecular cancer · 2026Article
- Hydrogels as Local Structural-Protective Platforms in Rheumatoid Arthritis: An Evidence-Graded Review Across the Synovium-Cartilage-Bone Axis.Gels (Basel, Switzerland) · 2026Review
- A neutrophil-mesangial cell axis promotes glomerular injury in lupus nephritis.Annals of the rheumatic diseases · 2026Article
- Neutrophil extracellular traps in osteoporosis: mechanistic links to bone remodeling imbalance and therapeutic perspectives.Molecular biology reports · 2026Review
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Turmeric-derived nanovesicles reprogram pathological NETosis to mitigate inflammatory bone loss.Journal of nanobiotechnology · 2026Article
- Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mechanisms of monosodium urate crystal-induced bone destruction in gouty arthritis (Review).Biomedical reports · 2026Review
- Emodin Attenuates Rheumatoid Arthritis by Modulating the NF-κB/HIF-1α/VEGF Signaling Pathway.International journal of molecular sciences · 2026Article
- Histidine alleviates Hashimoto's thyroiditis via the neutrophil extracellular traps-NF-κB signaling pathway.Scientific reports · 2026Article
- Deficiency of interleukin-40 prevents intestinal damage in experimental necrotizing enterocolitis by inhibiting NETosis.Cell communication and signaling : CCS · 2026Article
- Neutrophils as critical orchestrators of chronic inflammation.Cellular & molecular immunology · 2026Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
objectiveNeutrophil infiltration into the synovial joint is a hallmark of rheumatoid arthritis (RA), a disease characterised by progressive bone erosion. However, the mechanisms by which neutrophils participate in bone destruction remain unclear. Carbamylation is a posttranslational modification linked to increased bone erosion in RA and we previously showed that carbamylation is present in RA neutrophil extracellular traps (NETs). However, it remains unclear whether NETs and their carbamylated protein cargo directly promote bone destruction and alter osteoclast biology.
methodsNETs and carbamylated NETs (cNETs) were assessed for their capacity to induce osteoclast formation in CD14+ monocytes. Chemical inhibitors and neutralising antibodies were used to elucidate the pathway by which NETs induce osteoclastogenesis. HLA-DRB1*04:01 mice received intra-articular injection of cNETs for 4 weeks. Joints were isolated and assessed for osteoclast formation. Plasma and synovial fluid samples from patients with RA (n=32) were assessed for the presence of carbamylated histone, and correlations to disease specific outcomes were performed.
resultsWe found that NETs, when cNETs, instruct monocytes to undergo rapid osteoclast formation. NET-mediated osteoclastogenesis appears to depend on Toll-like receptor 4 signalling and NET-associated proteins including histones and neutrophil elastase. In vivo, we identified that the number of osteoclasts increased following immunisation with cNETs in HLA-DRB1*04:01 transgenic mice. Furthermore, carbamylated histones are increased in plasma and synovial fluid from patients with RA and correlate with active bone resorption and inflammatory markers.
conclusionsOur results suggest that NETs have a direct role in RA-associated bone erosion by promoting osteoclast formation.
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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.