Exosomes from LPS-pretreated BMSCs treated periodontitis via improving oxidative stress

BACKGROUND: Research indicates that the occurrence of periodontitis is related to oxidative stress and mitochondrial dysfunction. Alleviating oxidative stress and mitochondrial dysfunction may be a promising treatment strategy for periodontitis. In this study, bone marrow mesenchymal stem cells (BMSCs) were pretreated with lipopolysaccharide (LPS), and their derived exosomes (LPS-BMSCs-Exo) were extracted. In vitro and in vivo experiments were conducted to study the therapeutic effects of alleviating oxidative stress, mitochondrial disorders, and periodontitis. METHODS: BMSCs were pretreated with LPS, and LPS-BMSCs-Exo were extracted and identified via transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. The biosafety of the exosomes was assessed through CCK-8, migration, and uptake assays. A cell oxidative stress model was established and treated with BMSCs-Exo or LPS-BMSCs-Exo, the following tests were performed: the effects of the two types of exosomes on the oxidative stress of periodontal ligament stem cells (PDLSCs) were determined, the mitochondrial state and the membrane potential were detected, the content of adenosine triphosphate (ATP) was determined, apoptosis was detected, and the effect of the exosomes on the osteogenic ability of the PDLSCs was detected. A periodontitis rat model was established, and PBS, BMSCs-Exo, and LPS-BMSCs-Exo were administered separately. Micro-CT, HE staining, Masson staining, immunohistochemistry, and ROS fluorescence staining were used to evaluate the therapeutic effect of each group on periodontitis in rats. RESULTS: The proposed LPS-BMSCs-Exo exhibits characteristics similar to those of exosomes, can be successfully taken up and internalized by PDLSCs, and promotes the proliferation and migration of these cells. LPS-BMSCs-Exo can effectively improve the oxidative stress state, alleviate mitochondrial dysfunction in cells, increase membrane potential, enhance ATP content, reduce apoptosis, and improve the osteogenic ability of PDLSCs. Micro-CT data revealed that alveolar bone-related indicators were significantly increased after LPS-BMSCs-Exo treatment, which could reduce the degradation and inflammation of periodontal tissue in rats and alleviate their oxidative stress. CONCLUSION: LPS-BMSCs-Exo can significantly alleviate the oxidative stress and mitochondrial dysfunction caused by periodontitis in periodontal tissue, thereby reducing inflammation in periodontal tissue and alveolar bone resorption.