1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation.
Hyoeun JeonJungeun YuJung Me HwangHye-Won ParkJiyeon YuZee-Won LeeTaesoo KimJaerang RhoPublished in: Immune network (2022)
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.
Keyphrases
- bone loss
- signaling pathway
- induced apoptosis
- high glucose
- drug induced
- poor prognosis
- diabetic rats
- emergency department
- oxidative stress
- type diabetes
- endothelial cells
- drug delivery
- mouse model
- long non coding rna
- body composition
- adipose tissue
- postmenopausal women
- binding protein
- cell cycle arrest
- toll like receptor
- soft tissue