Aging is associated with increased prevalence and severity of pathogenic outcomes of periodontal disease, including soft tissue degeneration and bone loss around the teeth. Although lipopolysaccharide (LPS) derived from the key periodontal pathogen Porphyromonas gingivalis (Pg) plays an important role in the promotion of inflammation and osteoclastogenesis via toll-like receptor (TLR)4 signaling, its pathophysiological role in age-associated periodontitis remains unclear. This study investigated the possible effects of Pg-LPS on RANKL-primed osteoclastogenesis and ligature-induced periodontitis in relation to aging using young (2 months old) and aged (24 months old) mice. To the best of our knowledge, our results indicated that expression of TLR4 was significantly diminished on the surface of osteoclast precursors isolated from aged mice compared with that of young mice. Furthermore, our data demonstrated that the TLR4 antagonist (TAK242) dramatically decreased the numbers of tartrate-resistant acid phosphatase positive (TRAP+) osteoclasts differentiated from RANKL-primed young osteoclast precursors (OCPs) compared with those isolated from aged mice in response to Pg-LPS. In addition, using a ligature-induced periodontitis mouse model, we demonstrated that Pg-LPS elevated (1) secretion of senescence-associated secretory phenotype (SASP) markers, including the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, as well as osteoclastogenic RANKL, and (2) the number of OCPs and TRAP+ osteoclasts in the periodontal lesion induced in young mice. In contrast, Pg-LPS had little, or no, effect on the promotion of periodontitis inflammation induced in aged mice. Altogether, these results indicated that periodontal disease in older mice occurs in a manner independent of canonical signaling elicited by the Pg-LPS/TLR4 axis.

衰老与牙周病致病结果的患病率和严重程度增加有关，包括软组织退化和牙齿周围的骨质流失。尽管源自关键牙周病原体牙龈卟啉单胞菌( Pg ) 的脂多糖 (LPS) 通过 toll 样受体 (TLR)4 信号传导在促进炎症和破骨细胞生成中发挥重要作用，但其在与年龄相关的牙周炎中的病理生理作用仍不清楚。本研究调查了Pg的可能影响-LPS 对 RANKL 引发的破骨细胞生成和结扎诱导的牙周炎与使用年轻（2 个月大）和老年（24 个月大）小鼠的衰老有关。据我们所知，我们的结果表明，与年轻小鼠相比，从老年小鼠分离的破骨细胞前体表面上 TLR4 的表达显着降低。此外，我们的数据表明，与从老年小鼠中分离出的对Pg的反应相比，TLR4 拮抗剂 (TAK242) 显着降低了从 RANKL 引发的年轻破骨细胞前体 (OCP) 分化的抗酒石酸酸性磷酸酶阳性 (TRAP+) 破骨细胞的数量-脂多糖。此外，使用结扎诱导的牙周炎小鼠模型，我们证明了Pg-LPS 升高 (1) 衰老相关分泌表型 (SASP) 标志物的分泌，包括促炎细胞因子 TNF-α、IL-6 和 IL-1β，以及破骨细胞 RANKL，以及 (2)在年轻小鼠中诱导的牙周病变中的 OCPs 和 TRAP+ 破骨细胞。相比之下，Pg -LPS 对促进老年小鼠牙周炎炎症的作用很小或没有作用。总之，这些结果表明，老年小鼠牙周病的发生方式与Pg -LPS/TLR4 轴引发的典型信号无关。