Contribution ofPorphyromonas gingivalislipopolysaccharide to experimental periodontitis in relation to aging
Contribution ofPorphyromonas gingivalislipopolysaccharide to experimental periodontitis in relation to aging
复制标题
DOI：
10.1007/s11357-020-00258-1
复制
发表时间：
2020-08-26
期刊：
影响因子：
5.6
通讯作者：
Movila, Alexandru
中科院分区：
文献类型：
--
作者：
Akkaoui, Juliet;Yamada, Chiaki;Movila, Alexandru
衰老与牙周病致病结果的患病率和严重程度增加有关，包括牙齿周围的软组织变性和骨质流失。尽管源自关键牙周病原菌牙龈卟啉单胞菌 (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，但其在年龄相关性牙周炎中的病理生理学作用仍不清楚。本研究使用年轻（2 个月大）和老年（24 个月大）小鼠研究了 Pg-LPS 对 RANKL 引发的破骨细胞生成和结扎诱导的牙周炎与衰老相关的可能影响。据我们所知，我们的结果表明，与年轻小鼠相比，从老年小鼠中分离的破骨细胞前体表面的 TLR4 表达显着减少。此外，我们的数据表明，与从老年小鼠中分离的对 Pg-LPS 反应的破骨细胞相比，TLR4 拮抗剂 (TAK242) 显着减少了由 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。此外，使用结扎诱导的牙周炎小鼠模型，我们证明Pg-LPS可以提高（1）衰老相关分泌表型（SASP）标记物的分泌，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OCP和TRAP+破骨细胞的数量。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。总而言之，这些结果表明老年小鼠的牙周病以独立于 Pg-LPS/TLR4 轴引发的经典信号传导的方式发生。
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 pathogenPorphyromonas 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 ofPg-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 toPg-LPS. In addition, using a ligature-induced periodontitis mouse model, we demonstrated thatPg-LPS elevated (1) secretion of senescence-associated secretory phenotype (SASP) markers, including the pro-inflammatory cytokines TNF-alpha, IL-6, and IL-1 beta, 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 thePg-LPS/TLR4 axis.