Phosphatase and tensin homologue determine inflammatory status by differentially regulating the expression of Akt1 and Akt2 in macrophage alternative polarization of periodontitis

• Published in: Journal of clinical periodontology 2023-02, Vol.50 (2), p.220-231
• Main Authors: Wu, Xiaowei, Wang, Yidi, Chen, Haotian, Wang, Yixiang, Gu, Yan
• Format: Article
• Language: English
• Subjects: Akt1; AKT1 protein; Akt2; AKT2 protein; Alveolar bone; Alveolar Bone Loss; Animals; Bone resorption; Disease Models, Animal; Gum disease; Humans; Inflammation; macrophage polarization; Macrophages; Macrophages - metabolism; Mice; Microenvironments; NF-kappa B - metabolism; Periodontitis; Periodontitis - metabolism; Periodontium; Phosphatase; Polarization; Proto-Oncogene Proteins c-akt - metabolism; PTEN; PTEN Phosphohydrolase - metabolism; PTEN protein; Regeneration; Tensin
• ISSN: 0303-6979; 1600-051X
• DOI: 10.1111/jcpe.13730

Aim 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. Materials and Methods 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. Results 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. Conclusions 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.