Citropten Ameliorates Osteoclastogenesis Related to MAPK and PLCγ/Ca2+ Signaling Pathways through the Regulation of Amyloid Beta

Osteoporosis and Alzheimer's disease are typical types of dementia in seniors, which share common risk factors. Previous studies have shown that citizens with osteoporosis are more likely than healthy individuals to be at risk of Alzheimer's disease. Citropten, found in Citrus aurantifolia, has been reported to have several pharmacological activities; however, its antiosteoclastogenic activity remains unknown. Here, receptor activator nuclear factor.B ligand (RANKL)-induced osteoclast differentiation, formation, and function in the presence of amyloid beta (A ss) were attenuated by citropten in the RAW 264.7 cell line. The expression of osteoclast specific genes and proteins indicated that citropten pretreatment lowers the MAPK and PLC gamma/Ca2+ signaling pathways. Molecular docking simulations revealed that citropten interacts with the active sites of proteins in the calcium signaling pathway, which have negative binding affinities. These findings indicate that, through A ss regulation, the RANKLinduced osteoclast can be suppressed by citropten, suggesting that citropten is a potential candidate for treating osteoclastogenesisrelated diseases.