Isoschaftoside Inhibits Osteoclastogenesis by Suppressing the NF-κB and MAPK Pathways

Bone remodeling is regulated by the equilibrium between bone formation and resorption. However, excessive bone resorption by osteoclasts disrupts bone homeostasis and contributes to several bone-related disorders. Hematopoietic lineage cells differentiate into multinucleated osteoclasts through osteoclastogenesis, a process driven by M-CSF and RANKL. Multiple signaling pathways are involved in osteoclast maturation. RANKL-induced activation of NF-κB has been recognized as a crucial mechanism in osteoclast differentiation. Additionally, MAPK signaling activated by RANKL plays a significant role in this process. The stimulation of NF-κB and MAPK by RANKL enhances the transcription of numerous genes associated with osteoclastogenesis. Isoschaftoside (ISH), a C-glycosyl flavonoid, can be isolated from Viola yedoensis. The herb Viola yedoensis has traditionally been used to manage inflammation-related diseases, and its crude extracts have demonstrated pharmacological effects. Nonetheless, the influence of ISH on osteoclastogenesis has not been documented previously. In this study, we explored the effect of ISH on osteoclastogenesis. Our findings indicate that ISH attenuates RANKL-induced activation of NF-κB and MAPK; moreover, ISH inhibits osteoclastogenesis and bone resorption stimulated by RANKL and M-CSF.