ArticleBone2020
Bone regeneration is mediated by macrophage extracellular vesicles.
Article in Bone, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
113 citing papers in PubMed, 1 synthesis or guideline pooled it, 189 citations in OpenAlex.
- Would Exosome Therapy be Effective for Bone Regeneration? Systematic Review and Meta-Analysis.Calcified tissue international · 2025Pooled it
- The Role of EVs in the Aging Hematopoietic System.Aging cell · 2026Review
- Review
- Engineering Biomimetic 3D Microenvironments for Extracellular Vesicle Programming Toward Clinical Translation.International journal of molecular sciences · 2026Review
- Therapeutic strategy for exosome-based bone regeneration to osteoporosis: Challenges and potential solutions.Journal of advanced research · 2026Review
- Beyond M1/M2: The Pivotal Role of Macrophage Metabolic Reprogramming in Chronic Bone Disease and Targeted Intervention.International journal of molecular sciences · 2026Review
- Recent progress in immunomodulation-based strategies for bone repair.Regenerative therapy · 2026Review
- Research progress on the effects of macrophage‑derived exosomes on muscle factors IGF‑1 and FGF‑2 mediating musculoskeletal crosstalk molecular signaling pathway on bone metabolism (Review).International journal of molecular medicine · 2026Review
- The Osteoimmunologic Basis of Biologic and Bioengineered Scaffolds in Fracture Healing.Bioengineering (Basel, Switzerland) · 2026Review
- Bone Marrow Immunometabolic Remodeling in Osteoporosis: From Systemic Risk Factors to Precision Intervention.International journal of general medicine · 2026Review
- Que/n-HA/PGCL microspheres orchestrate bone repair via context-dependent osteoimmune mechanisms: a transcriptomic dissection of direct and immune-mediated signaling.Frontiers in immunology · 2026Article
- Exosomes in Bone Generation and Repair: Focusing on Bone Microenvironmental Crosstalk and Engineering Biomaterial Designs.International journal of nanomedicine · 2026Review
- Macrophage-derived exosomal miR-466i-5p and miR-365-2-5p stimulated by BMP-2 promote osteogenesis.Journal of orthopaedic surgery and research · 2025Article
- Review
- Advances in extracellular vesicle-based nanomedicine for regenerative orthopaedics.Journal of nanobiotechnology · 2025Review
- Exosomes promise better bone regeneration.Regenerative therapy · 2025Review
- The Role of Extracellular Vesicles in Musculoskeletal Diseases.Journal of extracellular vesicles · 2025Review
- Beyond the Cardio-Renal-Metabolic Axis: Emerging Therapeutic Targets and Novel Mechanisms of Action of Flozins.Journal of clinical medicine · 2025Review
- The role of exosomes in immunopathology and potential therapeutic implications.Cellular & molecular immunology · 2025Review
- Research Progress on Biomaterials with Immunomodulatory Effects in Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Multiple local and systemic factors including inflammation influence bone regeneration. Several lines of evidence demonstrate that macrophages contribute to the immunological regulation of MSC and osteoblast function during bone regeneration. Recent studies demonstrate that macrophage polarization influences this regulatory process. In this manuscript, we investigated the paracrine functional role of naïve (M0), M1 and M2 polarized macrophage derived EVs in bone repair. Treatment of rat calvaria defects with no EVs, M0 EVs, M1 EVs, or M2 EVs revealed polarization-specific control of bone regeneration by macrophage EVs at 3 and 6 weeks. M0 and M2 EVs promoted repair/regeneration and M1 EVs inhibited bone repair. Pathway-specific studies conducted in cell culture showed that M1 EVs negatively regulated the BMP signaling pathway, specifically BMP2 and BMP9. In parallel, miRNA sequencing studies showed similar miRNA cargo in M0 and M2 EVs and different miRNA cargo in M1 EVs. Functional examination of M1 macrophage EV-enriched miR-155 demonstrated that miR-155 mimic treatment reduced MSC osteogenic differentiation as measured by reduced BMP2, BMP9 and RUNX2 expression when compared to controls. Conversely, treatment of MSCs with the M2 macrophage EV-enriched miR-378a mimic increased MSC osteoinductive gene expression when compared to controls. These functional studies implicate polarized macrophage EV miRNAs in the positive or negative regulation of bone regeneration that was observed in vivo. Overall, the results presented in this study indicate that macrophage polarization influences EV cargo and related EV function in the paracrine regulation of bone regeneration.
Indexed as
Identifiers
What OpenQuestion holds
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.