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Extracellular Vesicles From LPS‐Treated PDLSCs Induce NLRP3 Inflammasome Activation in Periodontitis

Published:9 December 2024 DOI: 10.1111/odi.15210 PMID: 39652816
Yeke Wu,?Jiawei Li,?Min Liu,?Ranran Gao,?Hongling Zhou,?Qiongying Hu,?Lixing Zhao,?Yunfei Xie

Abstract

Objective: This study aimed to investigate the effects of lipopolysaccharide (LPS)-pretreated primary periodontal ligament stem cell (PDLSC)-derived extracellular vesicles (EVs) (L-PDLSC-EVs) on periodontitis.

Materials and methods: PDLSCs were obtained from mouse periodontal ligaments via enzymatic digestion. An in?vitro inflammatory microenvironment for PDLSCs was established using LPS, and L-PDLSC-EVs were isolated through ultracentrifugation and identified. EVs from different treatments were co-incubated with RAW264.7 macrophages (Mφs) or periodontal ligament fibroblasts (PLFs) and their co-cultures, whereafter the biological behaviors in Mφs and PLFs were evaluated. Periodontitis mouse models were established to verify the role of L-PDLSC-EVs and the mechanisms involved.

Results: There were no significant changes in the characteristics of L-PDLSC-EVs compared with control EVs. L-PDLSC-EVs promoted M1-type Mφ polarization and activated the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome. Furthermore, L-PDLSC-EVs promoted PLF cytotoxicity and apoptosis by enhancing the M1 polarization of Mφs. In periodontitis mouse models, L-PDLSC-EVs facilitated alveolar bone loss, PLF injury, and inflammatory responses, accompanied by an increased proportion of M1-type Mφs and reinforced NLRP3 inflammasome activation.

Conclusions: L-PDLSC-EVs promoted PLF injury and exacerbated periodontitis through activating the NLRP3 inflammasome and promoting the polarization of M1-type Mφs, providing novel insights for the periodontitis progression.

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