Piezo1/PI3K-induced autophagy dysregulation in PDLSCs under mechanical stress during root resorption

This study aimed to clarify the mechanobiological mechanisms of physiological root resorption in deciduous teeth, focusing specifically on how mechanical stress influences autophagy in periodontal ligament stem cells (PDLSCs) via the Piezo1 ion channel. We established a unilateral occlusal loading model in mice to simulate physiological mechanical stress, while in vitro studies utilized PDLSCs isolated from deciduous teeth at different resorption stages. Techniques included immunofluorescence staining for autophagy markers, Western blot analysis, Piezo1-specific pharmacological modulation, and transcriptome sequencing. Conditional Piezo1 knockout mice were generated to validate the mechanotransduction pathway. Our findings revealed distinct stage-dependent patterns in PDLSC behavior: early resorption stage (S-stage) cells maintained high autophagic activity with low IL-1β secretion, while mid-resorption stage (M-stage) cells showed Piezo1 upregulation and autophagy suppression. Mechanical stress was shown to inhibit autophagy through Piezo1-mediated activation of the PI3K/AKT pathway. Transgenic mouse models confirmed Piezo1's essential role in mediating mechanical stress responses in periodontal tissue. The study establishes Piezo1 as a critical mechanotransducer that coordinates stage-specific autophagy regulation in PDLSCs through the PI3K/AKT signaling pathway. These findings suggest that controlled modulation of mechanical forces or Piezo1 activity could offer new therapeutic strategies for managing deciduous tooth exfoliation. KEY MESSAGES: Mechanical stress inhibits PDLSC autophagy via Piezo1/PI3K/AKT pathway. Piezo1 is key for mechanosensing in periodontal tissue remodeling. Targeting mechano-autophagy may regulate deciduous root resorption.