International Journal of Nanomedicine (Sep 2023)
Periodontal Ligament Stem Cell Exosomes Key to Regulate Periodontal Regeneration by miR-31-5p in Mice Model
Abstract
Jiuqing Lu,1,2,* Nijia Yu,1,* Qian Liu,2,* Yajia Xie,1 Lei Zhen2 1Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhen, Department of Stomatology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel +86 1 582 108 9038, Email [email protected]: Periodontitis is a chronic inflammatory disease that causes alveolar bone loss. Diabetes is one of the most important factors contributing to periodontitis. Exosomes derived from mesenchymal stem cells (MSCs-Exo) have been reported to promote bone regeneration. This study aimed to examine the function and mechanism of exosomes derived from periodontal ligament stem cells (PDLSCs-Exo) in regulating periodontal regeneration in diabetic periodontitis.Methods: Exosomes derived from normal-glucose-cultured PDLSCs (NG-PDLSCs-Exo) and high-glucose-preconditioned PDLSCs (HG-PDLSCs-Exo) were used. Their effects on RAW264.7 cells were investigated by TRAP staining and quantitative real time-polymerase chain reaction (qRT-PCR). The role of exosomal miR-31-5p in osteoclast differentiation was tested using qRT-PCR, double luciferase analysis, and Western blotting. We investigated the effects of these two types of PDLSCs-Exo on alveolar bone loss in vivo in mice with experimental periodontitis.Results: PDLSCs-Exo were transferred to RAW264.7, and HG-PDLSCs-Exo inhibited osteoclast formation to a lesser extent than NG-PDLSCs-Exo. Further studies revealed the effect of PDLSCs-Exo on osteoclastogenesis via the miR-31-5p/eNOS signaling pathway. In mice with experimental periodontitis, PDLSCs-Exo reduced alveolar bone destruction and decreased the number of osteoclasts on the alveolar bone surface.Conclusion: Our results suggest that exosomal miR-31-5p derived from PDLSCs regulates alveolar bone regeneration by targeting eNOS.Keywords: diabetes, periodontitis, macrophage, osteoclast differentiation
