Exosomes miR-92a-3p from human exfoliated deciduous teeth inhibits periodontitis progression via the KLF4/PI3K/AKT pathway.

Background: Periodontitis is a chronic inflammatory disease mediated by dysbiosis of the oral microflora, resulting in the destruction of periodontal tissue. Increasing evidence suggested that mesenchymal stem cell (MSCs) and exosomes derived from MSCs play a critical role in periodontal tissue regeneration. However, whether stem cells from exfoliated deciduous teeth (SHED)-secreted exosomes can improve the therapeutic potential of periodontitis is largely unknown.

Objective: Here, we aim to evaluate the effect of SHED-exosomes on inflammation, apoptosis and osteogenic differentiation in periodontitis.

Methods: The periodontitis cell model was constructed by stimulating periodontal ligament stem cells (PDLSCs) with lipopolysaccharide (LPS), and the periodontitis rats were established by ligation.

Results: First, we isolated exosomes from the SHED, and we figured out that exosomes secreted by SHED were enriched in miR-92a-3p and the exosomes enhanced proliferation and osteogenic differentiation and reduced apoptosis and inflammatory responses in PDLSCs. In addition, we found that SHED-exosomes alleviated inflammatory effect and elevated the expression of osteogenic-related genes in periodontitis rat model. Moreover, miR-92a-3p targeted downstream Krüppel-Like Transcription Factor 4 (KLF4) and regulated the PI3K/AKT pathway. Finally, our data indicated that upregulation of KLF4 or activation of PI3K/AKT by 740Y-P counteracted the inhibitory effect of SHED-exosomes on periodontitis progression.

Conclusion: Taken together, our finding revealed that exosomal miR-92a-3p derived from SHED contributed to the alleviation of periodontitis development and progression through inactivating the KLF4/PI3K/AKT signaling pathway, which may provide a potential target for the treatment of periodontitis.