ArticleActa biomaterialia2021
Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss.
Article in Acta biomaterialia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 288 papers, 3 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
288 citing papers in PubMed, 3 syntheses or guidelines pooled it, 431 citations in OpenAlex.
- Extracellular Vesicles for Treatment of Bone Resorption-Related Diseases in Animal Models: Systematic Review.Calcified tissue international · 2026Pooled it
- Unlocking the potential of stem cell-derived extracellular vesicles in osteoporosis therapy: a systematic review and meta-analysis of preclinical studies.Journal of translational medicine · 2025Pooled it
- Mesenchymal stem cell-derived extracellular vesicles for treatment of bone loss within periodontitis in pre-clinical animal models: a meta-analysis.BMC oral health · 2023Pooled it
- Safety and efficacy of human gingiva-derived mesenchymal stem cells in patients with type 1 diabetes: a double-blind, randomized, placebo-controlled, phase 1 trial.Signal transduction and targeted therapy · 2026Trial
- Injectable Hydrogel Loaded With Umbilical Cord Blood-Derived Exosomes Promotes Periodontal Bone Regeneration via the TLR4/NF-κB Signalling Pathway.Journal of cellular and molecular medicine · 2026Article
- M2 polarization of macrophages: Manipulation of spinal cord injury repair.Neural regeneration research · 2026Article
- Exosomal export of activated CASPASE-8 is linked to the prevention of TNF-induced cytotoxicity.Nature communications · 2026Article
- [Frontier research on smart delivery biomaterials in the field of oral tissue engineering].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2026Review
- Applications and prospects of the immunomodulatory and regenerative capabilities of gingival mesenchymal stem cells for chronic inflammation treatment.Molecular biology reports · 2026Review
- Epigenetic modulation of the JAK2-STAT3 signaling pathway in osteoporosis: non-coding RNA networks as therapeutic targets.Journal of translational medicine · 2026Review
- Tissue derived extracellular vesicles advance from disease mechanisms to clinical application.Discover nano · 2026Review
- Exosomal microRNAs in Periodontitis: From Molecular Footprints to Clinical Frontiers.ACS pharmacology & translational science · 2026Review
- Advancing MSC-EV Therapies: Harnessing Preconditioning and Mito-EVs to Tackle Neuroinflammation and Neurodegeneration.Pharmaceutics · 2026Review
- Platelet-rich plasma cues program M2 macrophage-derived exosome mimetics to regenerate the tendon-bone interface.Journal of nanobiotechnology · 2026Article
- Transplantation of AQP1-overexpressing mitochondria attenuates periodontitis-associated bone loss by regulating mitochondria-ER contacts of macrophages.Journal of nanobiotechnology · 2026Article
- Evaluation of the antibacterial activity of stem cells from apical papilla and their conditioned medium against Escherichia coli and Staphylococcus aureus.Archives of microbiology · 2026Article
- 3D-embedding of human gingiva-derived mesenchymal stromal cells in "VitroGelBMC oral health · 2026Article
- Immunotherapies based on macrophage reprogramming in periodontitis and apical periodontitis.Clinical oral investigations · 2026Review
- Microenvironment-mediated stem cell fate in periodontal tissue remodeling and repair.Bioactive materials · 2026Review
- Beyond M1/M2: The Pivotal Role of Macrophage Metabolic Reprogramming in Chronic Bone Disease and Targeted Intervention.International journal of molecular sciences · 2026Review
228 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
Mesenchymal stem cell (MSC)-derived exosome plays a central role in the cell-free therapeutics involving MSCs and the contents can be customized under disease-associated microenvironments. However, optimal MSC-preconditioning to enhance its therapeutic potential is largely unknown. Here, we show that preconditioning of gingival tissue-derived MSCs (GMSCs) with tumor necrosis factor-alpha (TNF-α) is ideal for the treatment of periodontitis. TNF-α stimulation not only increased the amount of exosome secreted from GMSCs, but also enhanced the exosomal expression of CD73, thereby inducing anti-inflammatory M2 macrophage polarization. The effect of GMSC-derived exosomes on inflammatory bone loss were examined by ligature-induced periodontitis model in mice. Local injection of GMSC-derived exosomes significantly reduced periodontal bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and these effects were further enhanced by preconditioning of GMSCs with TNF-α. Thus, GMSC-derived exosomes also exhibited anti-osteoclastogenic activity. Receptor activator of NF-κB ligand (RANKL) expression was regulated by Wnt5a in periodontal ligament cells (PDLCs), and exosomal miR-1260b was found to target Wnt5a-mediated RANKL pathway and inhibit its osteoclastogenic activity. These results indicate that significant ability of the TNF-α-preconditioned GMSC-derived exosomes to regulate inflammation and osteoclastogenesis paves the way for establishment of a therapeutic approach for periodontitis.
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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.