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.

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.