M2-Exo-derived miR-1227-5p protects against periodontitis through inhibiting USP2-dependent deubiquitination of Drp1

Periodontitis is a common chronic inflammatory disease with an exaggerated host immune response. M2 type macrophages exert protective properties in periodontitis. This study aimed to investigate the role of M2-Exo-derived miR-1227-5p in periodontitis. M2-Exo were verified using TEM and NTR assay. miRNA and mRNA levels were determined using RT-qPCR. periodontal ligament stem cells (PDLCs) were exposed to LPS in establish in vitro periodontitis model. Gene expression was determined using Western blot and immunofluorescence. The binding sites of miR-1227-5p on USP2 were predicted by TargetScan and verified by luciferase, RNA pull-down, and RIP assays. Deubiquitination of Drp1 was determined using in vitro ubiquitination assay. Cellular behaviors of PDLCs were analyzed by CCK-8, alizarin red staining, and ALP staining. LPS exposure induced mitochondrial dysfunction and suppressed the osteogenesis of PDLCs. M2-Exo-derived miR-1227-5p improved mitochondrial function and promoted the proliferation and osteogenesis of PDLCs. miR-1227-5p directly targeted USP2. USP2 overexpression reversed the effects of miR-1227-5p and improved mitochondrial function and the osteogenesis of PDLCs. Moreover, miR-1227-5p targeted USP2 to inhibit the deubiquitination of Drp1, improving mitochondrial function. Furthermore, M2-Exo-derived miR-1227-5p alleviates periodontitis via regulating USP2/Drp1. Therefore, M2-Exo hold great potential for future clinical applications.