ArticleJournal of inflammation research2021
The Role of Adenosine Receptor A2A in the Regulation of Macrophage Exosomes and Vascular Endothelial Cells During Bone Healing.
Article in Journal of inflammation research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Exosomes as Cellular Communicators and Therapeutic Agents in Orthopedic Diseases: From Mechanisms to Intervention.International journal of nanomedicine · 2026Pooled it
- Crosstalk Between H-Type Vascular Endothelial Cells and Macrophages: A Potential Regulator of Bone Homeostasis.Journal of inflammation research · 2025Review
- CD73-positive pediatric urethral mesenchymal stem-like cell-derived small extracellular vesicles stimulate angiogenesis.Regenerative therapy · 2024Article
- Non-bone-derived exosomes: a new perspective on regulators of bone homeostasis.Cell communication and signaling : CCS · 2024Review
- The Essential Role of Angiogenesis in Adenosine 2A Receptor Deficiency-mediated Impairment of Wound Healing Involving c-Ski via the ERK/CREB Pathways.International journal of biological sciences · 2024Article
- Multifunctional hydrogel enhances bone regeneration through sustained release of Stromal Cell-Derived Factor-1α and exosomes.Bioactive materials · 2023Article
- Extracellular adenosine signaling in bone health and disease.Current opinion in pharmacology · 2023Review
- Osteoimmune Interactions and Therapeutic Potential of Macrophage-Derived Small Extracellular Vesicles in Bone-Related Diseases.International journal of nanomedicine · 2023Review
- Long Non-Coding RNAs Within Macrophage-Derived Exosomes Promote BMSC Osteogenesis in a Bone Fracture Rat Model.International journal of nanomedicine · 2023Article
- Extracellular ATP and its derivatives provide spatiotemporal guidance for bone adaptation to wide spectrum of physical forces.Bone reports · 2022Review
- Biophysical Modulation of Mesenchymal Stem Cell Differentiation in the Context of Skeletal Repair.International journal of molecular sciences · 2022Review
- Research Progress of Exosomes in Bone Diseases: Mechanism, Diagnosis and Therapy.Frontiers in bioengineering and biotechnology · 2022Review
- The Extract ofDrug design, development and therapy · 2022Article
- Macrophage-Derived Small Extracellular Vesicles in Multiple Diseases: Biogenesis, Function, and Therapeutic Applications.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMacrophage exosomes and vascular endothelial cells (VECs) are critical to bone healing. However, few studies explore the molecular regulation of them in the bone fracture microenvironment.
methodsIn this study, we explored the effects of adenosine receptor A2A (ADA2AR) in macrophage exosomes and VECs during bone healing. CGS21680 (an ADA2AR agonist) and ZM241385 (an ADA2AR antagonist) were used. First, the effects of the ADA2AR on VECs during bone healing were studied in vivo in a rat tibial fracture model. Second, the effects of ADA2AR on VECs and in the regulation of VECs by macrophages were examined in the bone fracture microenvironment. Third, the effects of ADA2AR on the regulation of macrophage exosomes on VECs were analyzed. Finally, the genes and long non-coding RNAs (lncRNAs) associated with the regulation of VECs by the ADA2AR were examined by high-throughput sequencing and bioinformatics analysis.
resultsCGS21680 accelerated VEC proliferation in the early stage of bone healing and that ZM241385 suppressed VEC proliferation in vivo. ZM241385 inhibited cell viability and tube formation in vitro. However, CGS21680 did not promote tube formation, cell proliferation, or cell migration in vitro. The inhibition of macrophage exosomes could suppress tube formation and VEC migration. CGS21680 had no effects on tube formation in a macrophage-VEC co-culture. The macrophage exosomes were purified and CGS21680 promoted the macrophage secretion of exosomes. In contrast, ZM241385 inhibited the macrophage secretion exosomes. Finally, the lncRNA and mRNA involved in the activation of the ADA2AR in VECs were analyzed. CGS21680 upregulated 3274 mRNAs and downregulated 2236 mRNAs, and upregulated 1696 lncRNAs and downregulated 1882 lncRNAs. The hub genes involved in angiogenesis were
conclusionThe activation of ADA2AR was essential for angiogenesis and the secretion of exosomes by macrophages during bone healing; moreover, the inactivation of the ADA2AR led to poor angiogenesis and bone nonunion.
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