ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2024
Increased neutrophil extracellular traps caused by diet-induced obesity delay fracture healing.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Neutrophils: The Overlooked Regenerative Role in Bone Repair.Stem cell reviews and reports · 2026Review
- Dietary omega-6 lipids promote postinjury aberrant bone formation in obesity.The Journal of clinical investigation · 2026Article
- The Role of Plastin in Bone, Cartilage, and Related Diseases.Calcified tissue international · 2026Review
- Does body mass index independently affect functional outcomes after conservatively treated distal radius fractures? a retrospective cohort study.BMC musculoskeletal disorders · 2026Article
- Immune and metabolic remodeling following bariatric surgery: Implications for targeted immunotherapy (Review).International journal of molecular medicine · 2026Review
- ZIF-8-Based Nanomedicine for Bone Regeneration: A Critical Appraisal of Preclinical Osteoimmunomodulatory Evidence and Translational Readiness.International journal of nanomedicine · 2026Review
- Physical cues influence the construction of the osteoimmune microenvironment: focus on the hematoma period.Regenerative biomaterials · 2026Review
- NLRP3 Inflammasome-Mediated Pyroptosis in Osteoporosis: Osteoimmune Mechanisms and Therapeutic Targeting.Journal of cellular and molecular medicine · 2025Review
- CitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.Pharmaceutics · 2025Review
- Associations between an inflammatory diet index and nonunion: a prospective study of 172,839 UK biobank participants.Frontiers in nutrition · 2025Article
- Mitochondrial metabolic regulation of macrophage polarization in osteomyelitis and other orthopedic disorders: mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Increased neutrophil extracellular traps caused by diet-induced obesity delay fracture healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Obesity, recognized as a risk factor for nonunion, detrimentally impacts bone health, with significant physical and economic repercussions for affected individuals. Nevertheless, the precise pathomechanisms by which obesity impairs fracture healing remain insufficiently understood. Multiple studies have identified neutrophil granulocytes as key players in the systemic immune response, being the predominant immune cells in early fracture hematomas. This study identified a previously unreported critical period for neutrophil infiltration into the callus. In vivo experiments demonstrated that diet-induced obesity (DIO) mice showed earlier neutrophil infiltration, along with increased formation of neutrophil extracellular traps (NETs), compared to control mice during the endochondral phase of fracture repair. Furthermore, Padi4 knockout was found to reduce NET formation and mitigate the fracture healing delays caused by high-fat diets. Mechanistically, in vitro analyses revealed that NETs, by activating NLRP3 inflammasomes, inhibited the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and concurrently promoted M1-like macrophage polarization. These findings establish a connection between NET formation during the endochondral phase and delayed fracture healing, suggesting that targeting NETs could serve as a promising therapeutic approach for addressing obesity-induced delays in fracture recovery.
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Registered trials
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