Exendin-4 Reduces Senescence of Inflammation-Induced Periodontal Ligament Stem Cells Through SIRT1/Notch1 Signaling

Periodontitis is a persistent inflammatory ailment that impacts periodontal tissues. Periodontal ligament stem cells (PDLSCs), also referred to as stem cells, possess advantageous attributes for tissue engineering and regenerative medicine due to their ability to self-renew with multi-directional differentiation potential. Nevertheless, the process of cellular senescence can compromise the restoration and regeneration of tissues, thereby impairing the normal regenerative and reparative functions of the periodontium. Exendin-4 (Ex-4) has protective effects against cellular senescence and apoptosis, but the impact of Ex-4 on inflammation-induced senescence of PDLSCs is unknown. This study used lipopolysaccharide (LPS) to simulate an inflammatory microenvironment, and then assessed the effect of Ex-4 on PDLSC senescence within that environment. Initially, PDLSCs were isolated and characterized and then cultured with LPS or LPS and Ex-4. Results demonstrated that the LPS-induced inflammatory microenvironment produced premature senescence of PDLSCs, which was reversible by treatment with Ex-4. Potential mechanisms underlying the effect were evaluated with regard to senescence-associated molecular pathways, and results demonstrated senescence of PDLSCs to be associated with Sirtuin 1 down-regulation and Notch1 upregulation. Our findings suggest that Ex-4 may mitigate the inflammation-induced senescence of PDLSCs through the SIRT1/Notch1 signaling pathway.