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

Hyoeun Jeon; Jungeun Yu; Jung Me Hwang; Hye-Won Park; Jiyeon Yu; Zee-Won Lee; Taesoo Kim; Jaerang Rho

doi:10.4110/in.2022.22.e43

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

Immune Netw. 2022 Sep 26;22(5):e43. doi: 10.4110/in.2022.22.e43. eCollection 2022 Oct.

Authors

Hyoeun Jeon¹, Jungeun Yu¹, Jung Me Hwang², Hye-Won Park¹, Jiyeon Yu¹, Zee-Won Lee³, Taesoo Kim⁴, Jaerang Rho¹

Affiliations

¹ Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Korea.
² Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Korea.
³ bHLBIO, Cheongju 28119, Korea.
⁴ Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.

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: 1,3-Dibenzyl-5-fluorouracil; Osteoclastogenesis; Osteoclasts; Osteoporosis; Ovariectomy.