Apelin‐12 Attenuates LPS‐Induced Cellular Senescence in Human Dental Pulp Cells via SIRT6‐Mediated Pathways: Implications for Gingivitis Management

Microbial infections and lipopolysaccharide (LPS)‐induced senescence in human dental pulp cells (hDPCs) play a significant role in gingivitis etiology. However, the role of Apelin‐12 in oral diseases, particularly its modulation of cellular senescence, remains poorly understood. This study investigated the protective effects of Apelin‐12 against LPS‐induced cellular senescence in hDPCs and its underlying mechanisms using cell isolation, culture, treatment, and transduction techniques, combined with reverse transcription‐polymerase chain reaction (RT‐PCR), Western blotting, telomerase activity assays, senescence‐associated β‐galactosidase (SA‐β‐Gal) staining, and gene silencing. We first confirmed apelin receptor (APJ) expression in hDPCs and found that LPS significantly downregulated APJ at both mRNA and protein levels. Apelin‐12 treatment restored telomerase activity and upregulated human telomerase reverse transcriptase (hTERT), while reducing senescence markers, including γH2AX and SA‐β‐Gal. Additionally, Apelin‐12 suppressed the expression of senescence regulators p21 and acetylated p53 (ac‐p53). Mechanistically, Apelin‐12 restored SIRT6 (but not SIRT1) expression, and silencing SIRT6 abolished its anti‐senescence effects, as evidenced by elevated p21, ac‐p53, and SA‐β‐Gal, along with reduced hTERT and telomerase activity. These findings demonstrate that Apelin‐12 attenuates LPS‐induced cellular senescence in hDPCs via SIRT6‐mediated pathways, suggesting its therapeutic potential for gingivitis management.