Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, People's Republic of China.
Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology, Shanghai, People's Republic of China.
J Clin Periodontol. 2023 Feb;50(2):220-231. doi: 10.1111/jcpe.13730. Epub 2022 Oct 18.
Macrophages are closely involved in periodontitis. However, the molecular mechanism by which macrophages influence periodontitis is not well understood. We investigated the effects of phosphatase and tensin homologue (PTEN) on macrophage polarization, the underlying mechanism and the regulatory roles in periodontium regeneration.
PTEN expression in periodontitis macrophages was detected ex vivo. The effects of PTEN on macrophage polarization and the underlying mechanisms were investigated in vitro. We also analysed the ability of PTEN inhibitors to repair periodontitis in vivo in a ligature-induced mouse model of periodontitis.
Macrophage PTEN expression in periodontitis patients was significantly higher than that of controls. PTEN inhibition in macrophages induced alternative macrophage polarization, whereas PTEN overexpression facilitated classical polarization. PTEN inhibition facilitated activation of Akt1 while inhibiting expression of Akt2. Furthermore, Akt2 overexpression could rescue the effects of PTEN inhibition on NF-κB. Treatment with a PTEN inhibitor significantly attenuated the local inflammatory status and prevented alveolar bone resorption in the mouse model.
Our findings suggest that PTEN inhibition could induce alternative macrophage polarization by differentially regulating Akt1 and Akt2. This also changed a pro-inflammatory microenvironment to an anti-inflammatory environment by subsequently regulating the expression of NF-κB, thereby attenuating inflammatory alveolar bone resorption induced by ligature.
巨噬细胞与牙周炎密切相关。然而，巨噬细胞影响牙周炎的分子机制尚不清楚。我们研究了磷酸酶和张力蛋白同源物（PTEN）对巨噬细胞极化的影响、潜在机制以及在牙周组织再生中的调节作用。
体外检测牙周炎巨噬细胞中 PTEN 的表达。研究了 PTEN 对巨噬细胞极化的影响及其潜在机制。我们还分析了 PTEN 抑制剂在结扎诱导的牙周炎小鼠模型中体内修复牙周炎的能力。
牙周炎患者的巨噬细胞 PTEN 表达明显高于对照组。巨噬细胞中 PTEN 的抑制诱导了替代型巨噬细胞极化，而 PTEN 的过表达促进了经典型极化。PTEN 抑制促进 Akt1 的激活，同时抑制 Akt2 的表达。此外，Akt2 的过表达可以挽救 PTEN 抑制对 NF-κB 的作用。用 PTEN 抑制剂治疗可显著减轻小鼠模型中的局部炎症状态并防止牙槽骨吸收。
我们的研究结果表明，PTEN 抑制通过差异调节 Akt1 和 Akt2 可诱导替代型巨噬细胞极化。这也通过随后调节 NF-κB 的表达将促炎微环境改变为抗炎环境，从而减轻结扎引起的炎症性牙槽骨吸收。
