Periodontitis accelerates STING-mediated bone remodeling during orthodontic tooth movement

Area of Science:

• Oral biology
• Immunology
• Periodontology

Background:

• Orthodontic tooth movement (OTM) involves inflammation and bone resorption.
• Periodontitis complicates OTM, intensifying inflammation and bone loss.
• The role of Stimulator of interferon genes (STING) in periodontitis-associated OTM was previously unknown.

Purpose of the Study:

• To investigate the role of STING in OTM under periodontitis conditions.
• To elucidate the molecular mechanisms linking STING activation to inflammation and bone resorption.
• To identify potential therapeutic targets for managing OTM in periodontitis patients.

Main Methods:

• Established a rat model of OTM with ligature-induced periodontitis.
• Utilized in vitro models with rat periodontal ligament fibroblasts (PDLFs) under mechanical and inflammatory stress.
• Manipulated STING activity using agonists, inhibitors (H151), and knockdown; employed RNA sequencing and co-immunoprecipitation followed by LC-MS/MS.

Main Results:

• STING activation in PDLFs increased pro-inflammatory cytokines (IL-1β, IL-6) and reduced osteogenesis markers (Runx-2).
• In periodontitis-OTM rats, STING upregulation correlated with increased inflammation and bone loss, which was ameliorated by H151.
• Identified Annexin A2 (Anxa2) as a novel STING interactor; Anxa2 knockdown suppressed STING-induced ER stress, inflammation, apoptosis, and NF-κB activation.

Conclusions:

• STING activation in PDLFs drives ER stress, inflammation, apoptosis, and suppressed osteogenesis, accelerating bone resorption during OTM in periodontitis.
• Annexin A2 acts as a functional intermediary, linking STING activation to NF-κB signaling.
• Targeting STING or Anxa2 may offer a therapeutic strategy to mitigate bone loss in periodontitis-affected OTM.