ArticleBone research2024
Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing.
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 30 papers.
What it found
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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.
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
30 citing papers in PubMed, 26 citations in OpenAlex.
- Skeletal stem and progenitor cell niche organization, regulation and repair.Reviews in endocrine & metabolic disorders · 2026Review
- Context-Dependent Roles of the Plexin-B Family Across Neurological, Oncological, Immune and Cardiovascular Disorders: Mechanisms and Therapeutic Implications.Life (Basel, Switzerland) · 2026Review
- Youthfulness of marrow AdipoqBone research · 2026Article
- IL-34 Regulates Macrophage Polarization and Bone Defect Healing in Aged Mice.International journal of molecular sciences · 2026Article
- A bioorthogonal nanoconcentrisome system for epigenetic and immunometabolic reprogramming of tissue regeneration in aged female rats.Nature communications · 2026Article
- Senescent BMSC-Derived Thbs1 Drives Inflammaging and Impairs Bone Regeneration by Suppressing PINK1/Parkin-Mediated Mitophagy in Macrophages.Aging cell · 2026Article
- Profiling the molecular and physiological effects of senolytic treatment on aged mice identifies immune, fibrotic and metabolic remodeling.Nature aging · 2026Article
- Zinc and metformin co-functionalized polyetheretherketone: A novel dental implant material tailored for the elderly.Journal of advanced research · 2026Article
- A Novel SIRT1 Activator Hydroxygenkwanin Alleviates Osteoporosis by Inhibiting Ferroptosis and Lactylation in Skeletal Stem/Progenitor Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Immunosenescence and Bone Homeostasis: From Mechanisms of Homeostasis Disruption to Therapeutic Opportunities in Age-Related Skeletal Disorders.International journal of molecular sciences · 2026Review
- A spatiotemporal atlas of senescence-associated secretory phenotype in fracture healing: stage-dependent mechanisms and therapeutic windows.Inflammation and regeneration · 2026Review
- Spatial multi-omics decoding of the fracture nonunion niche: from immune-vascular-skeletal crosstalk to precision regeneration.Frontiers in medicine · 2026Review
- Cellular senescence in musculoskeletal diseases: biological mechanisms and clinical implications.Theranostics · 2026Review
- Osteoimmune senescence in aging-related bone diseases.Frontiers in immunology · 2026Review
- Osteoimmune senescence in aging bone: from inflammaging dogma to cell-type-specific therapeutic windows.Frontiers in immunology · 2026Review
- AMPKα1 Deficiency in Macrophages Impairs Tendon Regeneration and Tendon Stem Cell Function via TNF-α-FBP2 Signaling.International journal of biological sciences · 2026Article
- Discovery and identification of semaphorin 4D as a bioindicator of high fracture incidence in type 2 diabetic mice with glucose control.Journal of advanced research · 2026Article
- Biomaterials targeting senescent cells for bone regeneration: State-of-the-art and future perspectives.Bioactive materials · 2025Review
- Immunosenescence and cancer: molecular hallmarks, tumor microenvironment remodeling, and age-specific immunotherapy challenges.Journal of hematology & oncology · 2025Review
- Gut Microbiota Modulates Obesity-Associated Skeletal Deterioration Through Macrophage Aging and Grancalcin Secretion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
Skeletal stem/progenitor cell (SSPC) senescence is a major cause of decreased bone regenerative potential with aging, but the causes of SSPC senescence remain unclear. In this study, we revealed that macrophages in calluses secrete prosenescent factors, including grancalcin (GCA), during aging, which triggers SSPC senescence and impairs fracture healing. Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair. Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence. Mechanistically, GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction, resulting in cellular senescence. Depletion of Plxnb2 in SSPCs impaired fracture healing. Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice. Thus, our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence, and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.
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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.