Serum Starvation Regulates Autophagy of Human Periodontal Ligament Cells Through Reactive Oxygen Species Mediated Adenosine Monophosphate-Activated Protein Kinase/Mechanistic Target of RAPAMYCIN Axis.

INTRODUCTION AND AIMS: Human periodontal ligament cells (hPDLCs) play a pivotal role in periodontal tissue remodelling, a process essential for orthodontic tooth movement (OTM). Autophagy, a survival mechanism under cellular stress, is induced by nutrient deprivation and impacts hPDLC function. This study aimed to explore the role of autophagy in the adaptive response of hPDLCs to nutritional stress, an environment simulating conditions during OTM. METHODS: Nutrient deprivation in hPDLCs was modelled through serum starvation. Autophagy levels and relevant markers were assessed using electron microscopy, protein assays, and gene expression analyses. Emphasis was placed on adenosine monophosphate-activated protein kinase (AMPK) signalling, specifically phosphorylation of AMPKα at Thr172, as a regulatory node in autophagy induction. Loss- and gain-of-function approaches were utilized to investigate the role of Thr172 in AMPK-mediated autophagy under nutrient stress. RESULTS: Findings indicated a marked increase in reactive oxygen species-mediated autophagy in hPDLCs under nutrient deprivation. This process was significantly regulated by AMPK activation through Thr172 phosphorylation, establishing AMPK as a critical factor in autophagy induction during cellular adaptation to nutritional stress. CONCLUSION: Nutritional stress enhances reactive oxygen species-mediated autophagy in hPDLCs via AMPK signalling, underscoring the role of autophagy in cellular adaptation during OTM. Targeting the AMPK pathway could provide novel insights for optimizing orthodontic treatment by leveraging cellular adaptive mechanisms. CLINICAL RELEVANCE: Understanding the molecular mechanisms underlying autophagy in hPDLCs opens potential therapeutic pathways to improve OTM outcomes. Modulating autophagy may lead to advances in orthodontic therapies that facilitate periodontal tissue remodelling, enhancing clinical effectiveness.