Zhao Junwei, Jiao Jilan, Chen Xin, Zhang Yuemeng, Chen Ting, Xie Jianhua, Ou Xiaoyan
The Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China; Jiangxi Province Key Laboratory of Oral Biomedicine, Nanchang, China; Jiangxi Province Clinical Research Center for Oral Diseases, Nanchang, China.
State Key Laboratory of Food Science and Resources, Nanchang University, No. 235 Nanjing East Road, Nanchang 330047, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113435. doi: 10.1016/j.intimp.2024.113435. Epub 2024 Nov 4.
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.
牙周炎被认为是一种慢性炎症性疾病，衰老已成为一个重要的危险因素。细胞衰老在衰老的生物学过程中起着关键作用。衰老相关分泌表型（SASP）的特征是一系列促炎因子、趋化因子和蛋白酶，这些是衰老细胞的标志性特征。这些因子共同改变局部环境，影响牙周膜干细胞（PDLSCs）的功能。原花青素B2（PB2）是低聚原花青素的主要二聚体，具有抗氧化、抗炎和抗癌特性。PB2对牙周炎发挥保护作用的分子机制仍不完全清楚。因此，本研究旨在探讨PB2在炎症环境中对PDLSCs成骨分化的影响及其潜在机制。为了模拟慢性炎症状态，用牙龈卟啉单胞菌脂多糖（Pg. LPS）刺激PDLSCs。研究结果表明，PB2显著减轻炎症反应，增强抗氧化酶活性，并上调由Pg. LPS刺激的PDLSCs的成骨分化。RNA测序（RNA-Seq）显示，Pg. LPS影响细胞周期、细胞衰老和NF-κB信号通路。相比之下，PB2处理减少了衰老细胞的数量，并降低了衰老相关蛋白和基因的表达。蛋白质免疫印迹分析证实，PB2还降低了CCR7的水平，并抑制了NF-κB信号通路。总之，PB2通过NF-κB信号通路靶向CCR7表达以抑制SASP，证明了其抗炎和成骨特性，使PB2成为牙周炎辅助治疗的一种有前景的治疗选择。
