Osteogenic-Preconditioned Dental Follicle Cell-Derived Extracellular Vesicles Attenuate Experimental Periodontitis by Modulating Macrophage Responses.
- 1Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, People's Republic of China.
- 2Department of Endodontics, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, 510182, People's Republic of China.
- 3State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Oral Regenerative Medicine, Engineering Research Center of Oral Translational Medicine Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China.
Abstract
Introduction
Therapeutic improvement of periodontitis with extracellular vesicles (EVs) requires strategic optimization, as EV contents vary across sources. The periodontium originates from dental follicle cells (DFCs) and osteogenic-inductive DFCs have shown benefits in treating periodontal disease. Therefore, this study investigated osteogenic-induced DFC-derived EVs (Os-EVs) for the treatment of periodontitis and their immune-regulatory mechanisms.Methods
EVs were isolated from DFCs cultured under osteogenic or standard conditions. Their morphology, protein composition and elemental content were characterized. In vitro, their regulatory effects on macrophages, including phagocytosis, migration, polarization, and proteomic changes were assessed. In vivo, a rat model of ligature-induced periodontitis was treated locally with Os-EVs or control EVs. Micro-CT, histological staining and gingival proteomics were used to evaluate therapeutic outcomes and mechanisms.Results
Osteogenic induction altered EV composition, possibly enriching immunoglobulin-related proteins and mineral elements. Os-EVs were efficiently internalized by macrophages, suppressed macrophage migration, and inhibited the differentiation of the pro-inflammatory phenotype. In vivo, Os-EVs significantly reduced gingival inflammation and alveolar bone loss compared to control EVs. Proteomic profiling of macrophages and gingival tissue revealed a decrease in pro-inflammatory phenotype macrophages, potentially related to the downregulation of proteasome-related proteins, indicating an underlying correlation between macrophagic phenotype and the ubiquitin-proteasome system.Conclusion
These findings highlight the importance of donor cell conditioning in optimizing the bioactivity of EV-based biomaterials and suggest the potential therapeutic value of Os-EVs for treating periodontitis. Future research should investigate these findings in more detail.
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BibTeX
@article{yi2026osteogenicpreconditioned,
title = {{Osteogenic-Preconditioned Dental Follicle Cell-Derived Extracellular Vesicles Attenuate Experimental Periodontitis by Modulating Macrophage Responses.}},
author = {Genzheng Yi and Feng Huang and Huixiao Yang and Wei Kuang and Ting Liao and Ting Zhong and Huilin Wu and Siyuan Zhang and Libin Zhou},
journal = {International journal of nanomedicine},
year = {2026},
month = oct,
doi = {10.2147/ijn.s636512},
url = {https://europepmc.org/article/MED/42948680},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Osteogenic-Preconditioned Dental Follicle Cell-Derived Extracellular Vesicles Attenuate Experimental Periodontitis by Modulating Macrophage Responses.
AU - Genzheng Yi
AU - Feng Huang
AU - Huixiao Yang
AU - Wei Kuang
AU - Ting Liao
AU - Ting Zhong
AU - Huilin Wu
AU - Siyuan Zhang
AU - Libin Zhou
PY - 2026
DA - 2026/10/23
JO - International journal of nanomedicine
DO - 10.2147/ijn.s636512
UR - https://europepmc.org/article/MED/42948680
AB - Introduction Therapeutic improvement of periodontitis with extracellular vesicles (EVs) requires strategic optimization, as EV contents vary across sources. The periodontium originates from dental follicle cells (DFCs) and osteogenic-inductive DFCs have shown benefits in treating periodontal disease. Therefore, this study investigated osteogenic-induced DFC-derived EVs (Os-EVs) for the treatment of periodontitis and their immune-regulatory mechanisms.Methods EVs were isolated from DFCs cultured under osteogenic or standard conditions. Their morphology, protein composition and elemental content were characterized. In vitro, their regulatory effects on macrophages, including phagocytosis, migration, polarization, and proteomic changes were assessed. In vivo, a rat model of ligature-induced periodontitis was treated locally with Os-EVs or control EVs. Micro-CT, histological staining and gingival proteomics were used to evaluate therapeutic outcomes and mechanisms.Results Osteogenic induction altered EV composition, possibly enriching immunoglobulin-related proteins and mineral elements. Os-EVs were efficiently internalized by macrophages, suppressed macrophage migration, and inhibited the differentiation of the pro-inflammatory phenotype. In vivo, Os-EVs significantly reduced gingival inflammation and alveolar bone loss compared to control EVs. Proteomic profiling of macrophages and gingival tissue revealed a decrease in pro-inflammatory phenotype macrophages, potentially related to the downregulation of proteasome-related proteins, indicating an underlying correlation between macrophagic phenotype and the ubiquitin-proteasome system.Conclusion These findings highlight the importance of donor cell conditioning in optimizing the bioactivity of EV-based biomaterials and suggest the potential therapeutic value of Os-EVs for treating periodontitis. Future research should investigate these findings in more detail.
SN - 1176-9114
SN - 1178-2013
ER -