Hesc-Evs Ameliorate Aging-Associated Periodontitis Through Txnip Downregulation

Periodontitis is a chronic inflammatory disorder marked by progressive periodontal tissue and alveolar bone destruction, ultimately leading to tooth loss. Emerging evidence suggests that the senescence of periodontal ligament stem cells (PDLSCs) is pivotal in periodontitis pathogenesis. hESC-EVs possess anti-senescence properties, making them promising biotherapeutics. This study aims to investigate the anti-senescence effects of hESC-EVs on PDLSCs and their therapeutic potential for periodontitis treatment. Primary PDLSCs were isolated from clinical periodontal tissue samples and characterized by flow cytometry. A replicative senescence model was established through serial passaging. Cellular senescence was assessed using SA-β-gal staining, cell cycle analysis, and detection of senescence-associated markers (p16, p21, p53). The functional recovery of senescent PDLSCs was evaluated through CCK-8 proliferation assays, Transwell migration assays, and osteogenic differentiation (ALP and Alizarin Red staining). Based on transcriptome sequencing results, TXNIP's role was examined via lentiviral knockdown/overexpression. In vivo, periodontitis models in young/aged C57BL/6 mice were used to evaluate hESC-EVs' therapeutic efficacy through micro-CT and histology. hESC-EVs effectively counteract PDLSC senescence by significantly downregulating senescence markers (p16/p21/ p53) and restoring proliferative, migratory, and osteogenic differentiation capacities through TXNIP inhibition. In vivo studies demonstrated that EV treatment effectively rejuvenated senescent PDLSCs, attenuated alveolar bone loss, and ultimately alleviated periodontitis was compared to untreated controls. This study provides evidence that hESC-EVs ameliorate periodontitis through TXNIP-mediated rejuvenation of senescent PDLSCs, offering novel regenerative therapy potential for age-related periodontitis.