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

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.

Emerging role of mesenchymal stem cell-derived extracellular vesicles in periodontal regeneration

“…gingivalis and a halting reduction in bone density compared to the control group. 50 , 51 , 52 This can be associated with the modified motif of biologically active substances within EVs. According to Zheng et al., PDLSCs undergoing preliminary treatment in the presence of 1 μg/mL LPS showed lower amounts of microRNA-155-5 (miR-155-5) and an increasing response to Sirtuin 1 within the exosomes they generated, which resulted in abatement of the inflammatory microenvironment.…”

Mechanisms and clinical application potential of mesenchymal stem cells-derived extracellular vesicles in periodontal regeneration

“…For example, the paracrine, regenerative, and repair capabilities of MSCs significantly enhanced after LPS pretreatment, which has emerged as a potential therapy for inflammatory diseases and tissue injury [44]. In periodontal regeneration, scholars have shown that EVs secreted from DFSCs after 250 ng/ml LPS preconditioning manifested better reduction in Porphyromonas gingivalis pathogenicity and inhibition of bone loss compared with the controls [45][46][47]. This may be related to the altered content of bioactive molecules in EVs.…”

The Applications and Potentials of Extracellular Vesicles from Different Cell Sources in Periodontal Regeneration

“…The relevant studies mainly focus on SCEVs. Huang et al showed that DFC-EVs, especially LPS-DFC-EVs, could reduce the number of P. gingivalis in the gingival tissues of mice with periodontitis, and the expression of IL-6 and IL-1β in gingiva and PDL [ 127 ]. Liu et al constructed a mouse model of palatal gingival defect.…”