Abstract
Aims
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 homolog (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 analyzed 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 inhibited expression of Akt2. Furthermore, Akt2 overexpression could rescue the effects of PTEN inhibition on NF-κB. Treatment with PTEN inhibitor significantly attenuated the local inflammatory status and prevented alveolar bone resorption in 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, and thereby attenuated inflammatory alveolar bone resorption induced by ligature.
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