Oleoylethanolamide Exhibits GPR119-Dependent Inhibition of Osteoclast Function and GPR119-Independent Promotion of Osteoclast Apoptosis
Hyun-Ju Kim*, Dong-Kyo Lee, Xian Jin, Xiangguo Che, and Je-Yong Choi*
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, BK21 PLUS KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 41944, Korea
Received November 6, 2019; Revised December 9, 2019; Accepted December 10, 2019.; Published online January 13, 2020.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

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 shRNAtransduced 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: apoptosis, cytoskeleton, G protein-coupled receptor 119, oleoylethanolamide, osteoclast

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31 March 2020 Volume 43,
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