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牙周膜细胞来源的小细胞外囊泡抑制牙龈卟啉单胞菌的致病性。

Dental follicle cells-derived small extracellular vesicles inhibit pathogenicity of Porphyromonas gingivalis.

机构信息

State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, China.

Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China School of Stomatology, Sichuan University, Chengdu, China.

出版信息

Oral Dis. 2023 Jul;29(5):2297-2309. doi: 10.1111/odi.14239. Epub 2022 May 13.

Abstract

OBJECTIVE

It aims to explore the effect of dental follicle cells-derived small extracellular vesicles (D-sEVs) with or without lipopolysaccharides (LPS) pretreating on the pathogenicity of Porphyromonas gingivalis (P. gingivalis).

METHODS

The antibacterial effects of D-sEV were evaluated by measuring the growth, biofilm formation, gingipains, and type IX secretion system (T9SS) expression of P. gingivalis. And the influence of D-sEV on P. gingivalis adhesion, invasion, cytotoxicity, and host immune response was examined in gingival epithelial cells (GECs). Then P. gingivalis treated with D-sEV was applied to investigate the pathogenicity in experimental periodontitis of mice.

RESULTS

It showed that both D-sEV and P. gingivalis LPS-pretreated D-sEV (L-D-sEV) could target P. gingivalis, inhibit their growth and biofilm formation, and hinder the attachment and invasion in GECs, therefore remarkably decreasing P. gingivalis cytotoxicity and the expression of IL-1β and IL-6 in GECs. In addition, they significantly reduced the expression of P. gingivalis virulence factors (gingipains and T9SS). In vivo, it showed that the bacteria in the gingiva were significantly decreased after sEV treatment. Meanwhile, less bone loss and fewer inflammatory cells infiltration and osteoclast formation in D-sEV and L-D-sEV groups.

CONCLUSION

Both D-sEV and L-D-sEV were proven to inhibit the pathogenicity of P. gingivalis and thus prevented the development of periodontitis.

摘要

目的

探讨牙周膜细胞来源的小细胞外囊泡(D-sEV)及其经脂多糖(LPS)预处理后对牙龈卟啉单胞菌(P. gingivalis)致病性的影响。

方法

通过测量 P. gingivalis 的生长、生物膜形成、牙龈蛋白酶和九型分泌系统(T9SS)表达来评估 D-sEV 的抗菌作用。并在牙龈上皮细胞(GECs)中研究 D-sEV 对 P. gingivalis 黏附、侵袭、细胞毒性和宿主免疫反应的影响。然后将用 D-sEV 处理的 P. gingivalis 应用于小鼠实验性牙周炎中,以研究其致病性。

结果

结果表明,D-sEV 和 LPS 预处理的 D-sEV(L-D-sEV)均可靶向 P. gingivalis,抑制其生长和生物膜形成,并阻碍 GECs 的黏附和侵袭,从而显著降低 P. gingivalis 细胞毒性和 GECs 中 IL-1β和 IL-6 的表达。此外,它们还显著降低了 P. gingivalis 毒力因子(牙龈蛋白酶和 T9SS)的表达。体内实验表明,经 sEV 处理后,牙龈中的细菌数量明显减少。同时,D-sEV 和 L-D-sEV 组的骨丢失减少,炎症细胞浸润和破骨细胞形成减少。

结论

D-sEV 和 L-D-sEV 均能抑制 P. gingivalis 的致病性,从而预防牙周炎的发生。

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