ArticleAging cell2024
Age-related changes to macrophage subpopulations and TREM2 dysregulation characterize attenuated fracture healing in old mice.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Prognostic value of serum estradiol and sclerostin for predicting fracture healing in postmenopausal women with osteoporotic vertebral compression fractures.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Article
- Immunosenescence and Bone Homeostasis: From Mechanisms of Homeostasis Disruption to Therapeutic Opportunities in Age-Related Skeletal Disorders.International journal of molecular sciences · 2026Review
- Macrophages on demand: How tissue trauma shapes their role.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2026Review
- Sequential polarization of macrophages: an immunomodulatory strategy for novel bone repair materials.Regenerative biomaterials · 2026Review
- The TREM2 paradox in fibrosis: a unified mechanism for opposite outcomes across organs.Frontiers in immunology · 2026Review
- Macrophages in osteoporotic fractures: from immunometabolic mechanisms to precision therapeutic approaches.Frontiers in endocrinology · 2025Review
- The human retroviral-like aspartic protease 1 (ASPRV1): From in vitro studies to clinical correlations.The Journal of biological chemistry · 2024Review
- Age-related changes to macrophage subpopulations and TREM2 dysregulation characterize attenuated fracture healing in old mice.Aging cell · 2024Article
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Authors and funding
7 authors.
Funding
Abstract
Fracture healing complications increase with age, with higher rates of delayed unions and nonunions and an associated increase in morbidity and mortality in older adults. Macrophages have a dynamic role in fracture healing, and we have previously demonstrated that age-related changes in macrophages are associated with attenuated fracture repair in old mice. Here, we provide a single cell characterization of the immune cells involved in the early phase of fracture healing. We show that there were multiple transcriptionally distinct macrophage subpopulations present simultaneously within the healing tissue. Fracture healing was attenuated in old mice compared to young, and macrophages from the fracture callus of old mice demonstrated a pro-inflammatory phenotype compared to young. Interestingly, Trem2 expression was decreased in old macrophages compared to young. Young mice lacking Trem2 demonstrated attenuated fracture healing and inflammatory dysregulation similar to old mice. Trem2 dysregulation has previously been implicated in other age-related diseases, but its role in fracture healing is unknown. This work provides a robust characterization of the macrophage subpopulations involved in fracture healing, and further reveals the important role of Trem2 in fracture healing and may be a potential driver of age-related inflammatory dysregulation. Future work may further examine macrophages and Trem2 as potential therapeutic targets for management of fracture repair in older adults.
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