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Updated: Nov 24, 2025
Isolation, Processing and Analysis of Murine Gingival Cells
Published on: July 2, 2013
Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal
Yuki Nakao1, Takao Fukuda2, Qunzhou Zhang3
1Department of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
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.
Insights
Preconditioning gingival mesenchymal stem cells (GMSCs) with tumor necrosis factor-alpha (TNF-α) enhances exosome therapy for periodontitis. These exosomes reduce inflammation and bone loss by targeting osteoclast formation.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Oral Biology
Background:
- Mesenchymal stem cell (MSC)-derived exosomes are promising for cell-free therapeutics.
- Exosome content can be modulated by preconditioning MSCs.
- Optimal preconditioning strategies for enhanced therapeutic potential remain unclear.
Purpose of the Study:
- To investigate the efficacy of tumor necrosis factor-alpha (TNF-α) preconditioning of gingival tissue-derived MSCs (GMSCs) for periodontitis treatment.
- To determine the effects of TNF-α-preconditioned GMSC-derived exosomes on inflammation and bone resorption in a periodontitis model.
Main Methods:
- Gingival tissue-derived MSCs (GMSCs) were preconditioned with TNF-α.
- Exosomes secreted from GMSCs were isolated and characterized.
- The therapeutic effects of GMSC-derived exosomes were evaluated in a ligature-induced periodontitis mouse model.
- Molecular mechanisms involving exosomal miR-1260b, Wnt5a, and RANKL were investigated.
Main Results:
- TNF-α preconditioning increased exosome secretion and exosomal CD73 expression in GMSCs.
- TNF-α-preconditioned GMSC-derived exosomes induced anti-inflammatory M2 macrophage polarization.
- Local injection of GMSC-derived exosomes significantly reduced periodontal bone resorption and osteoclast numbers.
- Exosomal miR-1260b was identified to target the Wnt5a-mediated RANKL pathway, inhibiting osteoclastogenesis.
Conclusions:
- TNF-α preconditioning is an effective strategy to enhance the therapeutic potential of GMSC-derived exosomes for periodontitis.
- GMSC-derived exosomes possess anti-inflammatory and anti-osteoclastogenic properties.
- These exosomes offer a promising cell-free therapeutic approach for periodontitis by modulating inflammation and bone remodeling.
