Wu Yeke, Li Jiawei, Liu Min, Gao Ranran, Zhou Hongling, Hu Qiongying, Zhao Lixing, Xie Yunfei
Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Oral Dis. 2025 Apr;31(4):1277-1289. doi: 10.1111/odi.15210. Epub 2024 Dec 9.
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.
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.
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.
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.
本研究旨在探讨脂多糖（LPS）预处理的原代牙周膜干细胞（PDLSC）来源的细胞外囊泡（EVs）（L-PDLSC-EVs）对牙周炎的影响。
通过酶消化从小鼠牙周膜中获取PDLSCs。使用LPS为PDLSCs建立体外炎症微环境，并通过超速离心分离和鉴定L-PDLSC-EVs。将不同处理的EVs与RAW264.7巨噬细胞（Mφs）或牙周膜成纤维细胞（PLFs）及其共培养物共同孵育，然后评估Mφs和PLFs中的生物学行为。建立牙周炎小鼠模型以验证L-PDLSC-EVs的作用及相关机制。
与对照EVs相比，L-PDLSC-EVs的特征无明显变化。L-PDLSC-EVs促进M1型Mφ极化并激活含核苷酸结合寡聚化结构域、富含亮氨酸重复序列和吡啉结构域的蛋白3（NLRP3）炎性小体。此外，L-PDLSC-EVs通过增强Mφs的M1极化促进PLF细胞毒性和凋亡。在牙周炎小鼠模型中，L-PDLSC-EVs促进牙槽骨吸收、PLF损伤和炎症反应，同时伴有M1型Mφ比例增加和NLRP3炎性小体激活增强。
L-PDLSC-EVs通过激活NLRP3炎性小体和促进M1型Mφ极化促进PLF损伤并加重牙周炎，为牙周炎进展提供了新的见解。
