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.

Apelin‐12 | cellular senescence | gingivitis | lipopolysaccharide (LPS) | SIRT6.