Schwann cell-derived extracellular vesicles promote periodontal tissue regeneration.
8 affiliations
- 1Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China.
- 2School of Medicine and Dentistry, Griffith University, QLD, 4222, Gold Coast, Australia.
- 3Department of Periodontology, Guiyang Hospital of Stomatology, Guiyang, 550002, GuiZhou, China.
- 4School of Medicine and Dentistry, Griffith University, QLD, 4222, Gold Coast, Australia. [email protected].
- 5Institute for Biomedicine and Glycomics, Griffith University, QLD,, 4222,, Gold Coast, Australia. [email protected].
- 6Australian Centre for Precision Health and Technology (PRECISE), Griffith University, QLD,, 4222,, Gold Coast, Australia. [email protected].
- 7Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China. [email protected].
- 8Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Institute of Stomatology, Nanjing University, Nanjing, China. [email protected].
Abstract
Periodontitis is a common chronic inflammatory disease worldwide, and conventional therapies control inflammation but fail to achieve predictable regeneration. The inferior alveolar nerve (IAN) is a key peripheral nerve that governs mandibular bone homeostasis, and its disruption precipitates bone metabolic imbalance and impaired repair. However, the dynamic behavior of Schwann cells (SCs), the principal glial cells of this neural axis, and their mechanistic influence on periodontal ligament stem cells (PDLSCs) remain elusive. We established a rat IAN transection model and found that denervation induced progressive alveolar bone deterioration and compromised the osteogenic capacity of resident PDLSCs. Correlation analyses revealed that this bone deterioration coincided with progressive SC depletion in periodontal tissue, suggesting a link between Schwann cell loss and PDLSC dysfunction. Transcriptomic profiling of denervated PDLSCs revealed that dysregulated AMPK/mTOR signaling and suppressed autophagy are mechanisms underlying osteogenic impairment. Co-culture with SCs restored PDLSC proliferation and osteogenic differentiation, with SC-derived extracellular vesicles (SC-EVs) as important paracrine mediators of this effect. Mechanistically, SC-EVs delivered rno-miR-210-5p, which targeted the DAP1 gene and suppressed its expression, thereby activating the AMPK/mTOR-autophagy axis and rescuing osteogenic potential. In a rat denervated mandibular defect model, SC-EVs significantly enhanced bone regeneration. Collectively, these findings suggest that Schwann cells and their EVs participate in the neural regulation of periodontal bone metabolism and may play an important role in periodontal regeneration.
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BibTeX
@article{zhang2026schwann,
title = {{Schwann cell-derived extracellular vesicles promote periodontal tissue regeneration.}},
author = {Ting Zhang and Jiaying Liu and Xiyue Wang and Yu Wu and Mengjia Wang and Shuyu Cheng and Rong Liu and Shuang Zhang and Yangheng Zhang and Yin Xiao and Yanan Zhu and Fuhua Yan},
journal = {Journal of nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04848-7},
url = {https://europepmc.org/article/MED/42907858},
note = {CC BY},
}
RIS
TY - JOUR
TI - Schwann cell-derived extracellular vesicles promote periodontal tissue regeneration.
AU - Ting Zhang
AU - Jiaying Liu
AU - Xiyue Wang
AU - Yu Wu
AU - Mengjia Wang
AU - Shuyu Cheng
AU - Rong Liu
AU - Shuang Zhang
AU - Yangheng Zhang
AU - Yin Xiao
AU - Yanan Zhu
AU - Fuhua Yan
PY - 2026
DA - 2026/07/01
JO - Journal of nanobiotechnology
DO - 10.1186/s12951-026-04848-7
UR - https://europepmc.org/article/MED/42907858
AB - Periodontitis is a common chronic inflammatory disease worldwide, and conventional therapies control inflammation but fail to achieve predictable regeneration. The inferior alveolar nerve (IAN) is a key peripheral nerve that governs mandibular bone homeostasis, and its disruption precipitates bone metabolic imbalance and impaired repair. However, the dynamic behavior of Schwann cells (SCs), the principal glial cells of this neural axis, and their mechanistic influence on periodontal ligament stem cells (PDLSCs) remain elusive. We established a rat IAN transection model and found that denervation induced progressive alveolar bone deterioration and compromised the osteogenic capacity of resident PDLSCs. Correlation analyses revealed that this bone deterioration coincided with progressive SC depletion in periodontal tissue, suggesting a link between Schwann cell loss and PDLSC dysfunction. Transcriptomic profiling of denervated PDLSCs revealed that dysregulated AMPK/mTOR signaling and suppressed autophagy are mechanisms underlying osteogenic impairment. Co-culture with SCs restored PDLSC proliferation and osteogenic differentiation, with SC-derived extracellular vesicles (SC-EVs) as important paracrine mediators of this effect. Mechanistically, SC-EVs delivered rno-miR-210-5p, which targeted the DAP1 gene and suppressed its expression, thereby activating the AMPK/mTOR-autophagy axis and rescuing osteogenic potential. In a rat denervated mandibular defect model, SC-EVs significantly enhanced bone regeneration. Collectively, these findings suggest that Schwann cells and their EVs participate in the neural regulation of periodontal bone metabolism and may play an important role in periodontal regeneration.
SN - 1477-3155
ER -