Procyanidin B2 targeted CCR7 expression to inhibit the senescence-associated secretory phenotype through the NF-κB pathway to promote osteogenic differentiation of periodontal ligament stem cells in periodontitis.

Periodontitis is recognized as a chronic inflammatory disease, with aging emerging as a significant risk factor. Cellular senescence plays a crucial role in the biological process of aging. The senescence-associated secretory phenotype (SASP) is characterized by a series of pro-inflammatory factors, chemokines, and proteases, which are hallmark characteristics of senescent cells. These factors collectively alter the local environment, impacting the function of periodontal ligament stem cells (PDLSCs). Procyanidin B2 (PB2), the main dimer of oligomeric procyanidins, possesses antioxidant, anti-inflammatory, and anti-cancer properties. The molecular mechanisms through which PB2 exerts its protective effects against periodontitis remain incompletely understood. Therefore, this research aimed to investigate the effects and underlying mechanisms of PB2 on the osteogenic differentiation of PDLSCs within an inflammatory environment. To simulate a chronic inflammatory condition, PDLSCs were stimulated with Porphyromonas gingivalis Lipopolysaccharide (Pg. LPS). The findings indicated that PB2 significantly alleviated the inflammatory responses, enhanced the activity of antioxidant enzymes, and upregulated the osteogenic differentiation of PDLSCs stimulated by Pg. LPS. RNA sequencing (RNA-Seq) revealed that Pg. LPS influenced the cell cycle, cellular senescence, and NF-κB signaling pathways. In contrast, PB2 treatment reduced the number of senescent cells and diminished the expression of senescence-associated proteins and genes. Western blot analysis verified that PB2 also decreased the levels of CCR7 and suppressed the NF-κB signaling pathways. In conclusion, PB2 targeted CCR7 expression to inhibit the SASP through NF-κB signaling pathway, demonstrating its anti-inflammatory and osteogenic properties, positioning PB2 as a promising therapeutic option for the adjuvant treatment of periodontitis.