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1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation

  • Hyoeun Jeon (Department of Microbiology and Molecular Biology, Chungnam National University) ;
  • Jungeun Yu (Department of Microbiology and Molecular Biology, Chungnam National University) ;
  • Jung Me Hwang (Center for Genomic Integrity, Institute for Basic Science) ;
  • Hye-Won Park (Department of Microbiology and Molecular Biology, Chungnam National University) ;
  • Jiyeon Yu (Department of Microbiology and Molecular Biology, Chungnam National University) ;
  • Zee-Won Lee (bHLBIO) ;
  • Taesoo Kim (Herbal Medicine Research Division, Korea Institute of Oriental Medicine) ;
  • Jaerang Rho (Department of Microbiology and Molecular Biology, Chungnam National University)
  • Received : 2022.03.15
  • Accepted : 2022.07.27
  • Published : 2022.10.31
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Abstract

Osteoclasts (OCs) are clinically important cells that resorb bone matrix. Accelerated bone destruction by OCs is closely linked to the development of metabolic bone diseases. In this study, we screened novel chemical inhibitors targeting OC differentiation to identify drug candidates for metabolic bone diseases. We identified that 1,3-dibenzyl-5-fluorouracil, also named OCI-101, is a novel inhibitor of osteoclastogenesis. The formation of multinucleated OCs is reduced by treatment with OCI-101 in a dose-dependent manner. OCI-101 inhibited the expression of OC markers via downregulation of receptor activator of NF-κB ligand and M-CSF signaling pathways. Finally, we showed that OCI-101 prevents ovariectomy-induced bone loss by suppressing OC differentiation in mice. Hence, these results demonstrated that OCI-101 is a good drug candidate for treating metabolic bone diseases.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and was funded by the Ministry of Education (NRF-2019R1A2C1084311, 2019M3F6A1109486 and 2022R1A2C1004076).

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