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The role of autophagy in SIM mediated anti-inflammatory osteoclastogenesis through NLRP3 signaling pathway

Yuting Cheng1,2, Wenjun Jin2, Lin Zheng2

  • 1Faculty of Dentistry, Prince of Songkla University, Hat Yai, Thailand.

Immunity, Inflammation and Disease
|January 25, 2024
PubMed
Abstract

Insights

Simvastatin (SIM) reduces inflammatory bone loss by suppressing osteoclastogenesis and modulating autophagy via the NLRP3 pathway. This research provides a basis for using SIM to treat peri-implantitis.

Area of Science:

  • Biomedical Science
  • Immunology
  • Cell Biology

Background:

  • Inflammatory bone resorption is a key factor in dental implant failure.
  • Simvastatin (SIM) exhibits anti-inflammatory properties and inhibits osteoclastogenesis.
  • The precise mechanism by which SIM alleviates inflammatory bone loss requires further investigation.

Purpose of the Study:

  • To investigate the role of autophagy and the NLRP3 signaling pathway in SIM's anti-inflammatory bone resorption effects.
  • To elucidate how SIM modulates these pathways to prevent bone loss.

Main Methods:

  • RAW264.7 cells were treated with lipopolysaccharide (LPS) and varying concentrations of SIM.
  • Osteoclast (OC) differentiation, formation, and activity were assessed.
  • Autophagosome formation was observed via transmission electron microscopy.
  • Western blot and RT-qPCR were used to analyze protein and gene expression related to autophagy and the NLRP3 pathway.

Main Results:

  • SIM decreased pro-inflammatory tumor necrosis factor-α and increased anti-inflammatory Interleukin-10.
  • SIM inhibited LPS-induced osteoclast differentiation, formation, bone resorption, and OC-specific markers.
  • SIM suppressed autophagy by downregulating key proteins (LC3II, Beclin1, ATG7) and NLRP3 pathway factors, while upregulating P62.

Conclusions:

  • Simvastatin attenuates inflammatory bone loss by reducing autophagy and inhibiting the NLRP3 signaling pathway.
  • These findings support the potential therapeutic application of SIM in managing peri-implantitis.
Keywords:
NLRP3Simvastatinautophagyinflammatory bone resorptionosteoclast

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