Periodontitis (PD) is a common inflammatory disease known to be closely associated with metabolic disorders, particularly hyperlipidemia. In the current study, we demonstrated that hypercholesterolemia is a predisposing factor in the development of PD. Logistic regression analysis revealed a strong positive correlation between PD and dyslipidemia. Data from in vivo (PD mouse model subjected to a high cholesterol diet) and in vitro (cholesterol treatment of gingival fibroblasts [GFs]) experiments showed that excess cholesterol influx into GFs potentially contributes to periodontal inflammation and, subsequently, alveolar bone erosion. Additionally, we compared the protective efficacies of cholesterol-lowering drugs with their different modes of action against PD pathogenesis in mice. Among the cholesterol-lowering drugs we tested, fenofibrate exerted the most protective effect against PD pathogenesis due to an increased level of high-density lipoprotein cholesterol, a lipoprotein involved in cholesterol efflux from cells and reverse cholesterol transport. Indeed, cholesterol efflux was suppressed during PD progression by downregulation of the apoA-I binding protein (APOA1BP) expression in inflamed GFs. We also demonstrated that the overexpression of APOA1BP efficiently regulated periodontal inflammation and the subsequent alveolar bone loss by inducing cholesterol efflux. Our collective findings highlight the potential utility of currently available cholesterol-lowering medications for the mitigation of PD pathogenesis. By targeting the acceleration of high-density lipoprotein-mediated cellular cholesterol efflux, a new therapeutic approach for PD may become possible.

中文翻译：

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加速 HDL 介导的胆固醇外排可缓解牙周炎


牙周炎 （PD） 是一种常见的炎症性疾病，已知与代谢紊乱（尤其是高脂血症）密切相关。在目前的研究中，我们证明了高胆固醇血症是 PD 发展的诱发因素。Logistic 回归分析显示 PD 与血脂异常之间存在很强的正相关关系。来自体内（高胆固醇饮食的 PD 小鼠模型）和体外（牙龈成纤维细胞 [GF] 的胆固醇治疗）实验的数据表明，过量的胆固醇流入 GF 可能会导致牙周炎症，进而导致牙槽骨侵蚀。此外，我们比较了降胆固醇药物的保护功效及其对小鼠 PD 发病机制的不同作用方式。在我们测试的降胆固醇药物中，非诺贝特对 PD 发病机制发挥了最大的保护作用，因为高密度脂蛋白胆固醇水平升高，高密度脂蛋白胆固醇是一种参与胆固醇从细胞外排和逆转胆固醇转运的脂蛋白。事实上，在 PD 进展过程中，通过下调发炎 GF 中 apoA-I 结合蛋白 （APOA1BP） 的表达来抑制胆固醇外排。我们还证明，APOA1BP 的过表达通过诱导胆固醇外排有效地调节牙周炎和随后的牙槽骨丢失。我们的集体研究结果强调了目前可用的降胆固醇药物在缓解 PD 发病机制方面的潜在效用。通过靶向加速高密度脂蛋白介导的细胞胆固醇外流，PD 的新治疗方法可能成为可能。