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Mechanical Force Triggers Macrophage Pyroptosis and Sterile Inflammation by Disrupting Cellular Energy Metabolism

Hao Tan1,2,3, Guoyin Yang1,2,3, Ye Zhu1,2,3

  • 1College of Stomatology, Chongqing Medical University, Chongqing 401147, China.

International Journal of Molecular Sciences
|April 17, 2025
PubMed

Insights

Orthodontic force triggers programmed cell death called pyroptosis in macrophages, causing sterile inflammation. Inhibiting a specific enzyme restored metabolic balance, reducing inflammation during tooth movement.

Area of Science:

  • Biomedical Engineering
  • Cell Biology
  • Immunology

Background:

  • Mechanical force drives tissue remodeling in orthodontic tooth movement (OTM).
  • Macrophage-mediated sterile inflammation and pyroptosis are key inflammatory processes.
  • The precise mechanisms linking orthodontic force to macrophage pyroptosis remain unclear.

Purpose of the Study:

  • To investigate how orthodontic force induces macrophage pyroptosis and sterile inflammation.
  • To elucidate the underlying molecular and metabolic mechanisms.
  • To identify potential therapeutic targets for modulating OTM.

Main Methods:

  • Established rat OTM and force-loaded macrophage models.
  • Analyzed macrophage pyroptosis and sterile inflammation markers.
  • Investigated macrophage energy metabolism, including lactate dehydrogenase A (LDHA) and pyruvate dehydrogenase (PDH) pathways.
  • Assessed the effect of inhibiting pyruvate dehydrogenase kinase 1 (PDK1).

Main Results:

  • Orthodontic force induced Caspase1-dependent pyroptosis in macrophages, activating sterile inflammation both in vivo and in vitro.
  • Mechanical force disrupted macrophage energy metabolism, causing LDHA/PDH imbalance and mitochondrial dysfunction.
  • Inhibiting PDK1 restored metabolic balance, alleviating pyroptosis and sterile inflammation in force-stimulated macrophages.

Conclusions:

  • Force-induced macrophage pyroptosis and sterile inflammation are critical in OTM.
  • Imbalances in LDHA/PDH ratio and mitochondrial dysfunction are key mechanistic drivers.
  • Targeting PDK1 offers a potential therapeutic strategy for OTM modulation.
Keywords:
energy metabolismmacrophagemechanical forceorthodontic tooth movementpyroptosissterile inflammation

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