Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Lipopolysaccharide (LPS)-Induced Autophagy Is Responsible for Enhanced Osteoclastogenesis

  • Sul, Ok-Joo (Department of Biological Sciences, University of Ulsan) ;
  • Park, Hyun-Jung (Department of Biological Sciences, University of Ulsan) ;
  • Son, Ho-Jung (Department of Biological Sciences, University of Ulsan) ;
  • Choi, Hye-Seon (Department of Biological Sciences, University of Ulsan)
  • Received : 2017.09.25
  • Accepted : 2017.10.16
  • Published : 2017.11.30
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Abstract

We hypothesized that inflammation affects number and activity of osteoclasts (OCs) via enhancing autophagy. Lipopolysaccharide (LPS) induced autophagy, osteoclastogenesis, and cytoplasmic reactive oxygen species (ROS) in bone marrow-derived macrophages that were pre-stimulated with receptor activator of nuclear $factor-{\kappa}B$ ligand. An autophagy inhibitor, 3-methyladenine (3-MA) decreased LPS-induced OC formation and bone resorption, indicating that autophagy is responsible for increasing number and activity of OCs upon LPS stimulus. Knockdown of autophagy-related protein 7 attenuated the effect of LPS on OC-specific genes, supporting a role of LPS as an autophagy inducer in OC. Removal of ROS decreased LPS-induced OC formation as well as autophagy. However, 3-MA did not affect LPS-induced ROS levels, suggesting that ROS act upstream of phosphatidylinositol-4,5-bisphosphate 3-kinase in LPS-induced autophagy. Our results suggest the possible use of autophagy inhibitors targeting OCs to reduce inflammatory bone loss.

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References

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