Human Umbilical Cord Mesenchymal Stem Cells-Derived Exosomes Attenuates Experimental Periodontitis in Mice Partly by Delivering miRNAs.

Introduction: Periodontitis is the most common non-communicable disease in humans. The main challenge in the treatment of periodontitis is to effectively control periodontal inflammation and promote tissue repair. Human umbilical cord mesenchymal stem cells-derived exosomes (hucMSCs-exo) have been reported to modulate inflammatory responses and promote tissue repairment mainly through miRNAs in several diseases. However, the effect of hucMSCs-exo on periodontitis remains unknown. In this study, we hypothesized that hucMSCs-exo could inhibit bone destruction in periodontitis mice. Methods: In this study, we constructed and characterized the exo@H drug delivery platform. Lipopolysaccharide was used to construct an inflammatory microenvironment in vitro to detect MC3T3-E1 cells proliferation and bone regeneration capacity. Ligation induced to construct an experimental periodontitis mouse model. The distance of the cement-enamel junction (CEJ) to the alveolar bone crest (ABC) was measured for bone resorption evaluation. Hematoxylin-eosin (H&E) staining and Tartrate resistant acid phosphatase (TRAP) staining were used to observe periodontal tissue changes. MicroRNA (miRNA) sequencing was used to detect differential genes and for bioinformatics analysis. Real-time quantitative polymerase chain reaction (qRT-PCR). WB assay and dual luciferase assay were used to further validate the screened differentially expressed miRNAs and the targeted binding relationship with the corresponding target genes. Results: We found that lyophilized hucMSCs-exo promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells, and showed more significant proliferative and osteogenic differentiation abilities in combination with the hydrogel ( Discussion: These results suggest that exo@H provides protection against periodontitis partly by delivering miRNAs to periodontal tissue. Our results confirm the feasibility of the exo@H delivery platform we constructed and the effectiveness of its use for periodontitis treatment, and this study provides a promising approach for the treatment of periodontitis via miRNA.