Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Oleoylethanolamide Exhibits GPR119-Dependent Inhibition of Osteoclast Function and GPR119-Independent Promotion of Osteoclast Apoptosis

  • Kim, Hyun-Ju (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 PLUS KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Lee, Dong-Kyo (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 PLUS KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Jin, Xian (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 PLUS KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Che, Xiangguo (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 PLUS KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University) ;
  • Choi, Je-Yong (Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 PLUS KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University)
  • Received : 2019.11.06
  • Accepted : 2019.12.10
  • Published : 2020.04.30
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Abstract

Oleoylethanolamide (OEA), a bioactive lipid in bone, is known as an endogenous ligand for G protein-coupled receptor 119 (GPR119). Here, we explored the effects of OEA on osteoclast differentiation, function, and survival. While OEA inhibits osteoclast resorptive function by disrupting actin cytoskeleton, it does not affect receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. OEA attenuates osteoclast spreading, blocks actin ring formation, and eventually impairs bone resorption. Mechanistically, OEA inhibits Rac activation in response to macrophage colony-stimulating factor (M-CSF), but not RANKL. Furthermore, the OEA-mediated cytoskeletal disorganization is abrogated by GPR119 knockdown using small hairpin RNA (shRNA), indicating that GPR119 is pivotal for osteoclast cytoskeletal organization. In addition, OEA induces apoptosis in both control and GPR119 shRNA-transduced osteoclasts, suggesting that GPR119 is not required for osteoclast apoptosis. Collectively, our findings reveal that OEA has inhibitory effects on osteoclast function and survival of mature osteoclasts via GPR119-dependent and GPR119-independent pathways, respectively.

Keywords

References

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