Epifriedelinol From Aster tataricus Suppresses Osteoclast Differentiation and Bone Resorption via MAPK‐Mediated Inhibition of NFATc1/c‐Fos in RAW264.7 and BMM Cells: An In Vitro Study

ABSTRACT Osteoporosis, characterized by excessive osteoclast‐mediated bone resorption, necessitates innovative therapies to overcome the limitations of current treatments. This study explores the effects of epifriedelinol (EFD), a triterpene obtained from Aster tataricus L.fil., on RANKL‐induced osteoclastogenesis in RAW264.7 cells and bone marrow‐derived macrophages. Concentrations up to 10 µM of EFD exhibited no cytotoxicity but strongly impeded RANKL‐induced osteoclast differentiation, as indicated by a decrease in TRAP‐positive multinucleated cells in both cell types. EFD at least partially inhibited the activation of the MAPK signaling pathways (ERK, JNK, p38) and suppressed key transcription factors NFATc1 and c‐Fos, essential for osteoclast‐specific gene expression (TRAP, RANK, MMP‐9, cathepsin K). Moreover, EFD reduced RANKL‐induced bone resorption in BMMs, demonstrating decreased resorption pit area in a dose‐dependent manner. These findings indicate that EFD inhibits osteoclast differentiation and function by targeting the MAPK‐mediated NFATc1/c‐Fos pathway, highlighting its potential as a natural treatment for osteoclast‐related disorders such as osteoporosis.