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.

中文翻译：

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1,3-二苄基-5-氟尿嘧啶通过抑制破骨细胞分化来预防卵巢切除术引起的骨丢失。

破骨细胞 (OC) 是临床上重要的细胞，可吸收骨基质。OC 加速骨破坏与代谢性骨病的发展密切相关。在这项研究中，我们筛选了针对 OC 分化的新型化学抑制剂，以确定代谢性骨病的候选药物。我们发现 1,3-二苄基-5-氟尿嘧啶，也称为 OCI-101，是一种新型的破骨细胞生成抑制剂。用 OCI-101 以剂量依赖的方式处理可减少多核 OC 的形成。OCI-101 通过下调 NF-κB 配体和 M-CSF 信号通路的受体激活剂来抑制 OC 标志物的表达。最后，我们发现 OCI-101 通过抑制小鼠 OC 分化来预防卵巢切除术引起的骨质流失。因此，