Asarinin Inhibits RANKL-Induced Osteoclast Differentiation by Targeting the p38/ERK-c-Fos-NFATc1 Axis
Zhang, L.; Xie, C.; Bao, X.; Li, X.; Velez, H.; Kasonga, A.; Deepak, V.
Show abstract
Excessive osteoclast formation is a key contributor to pathological bone loss in disorders such as osteoporosis and rheumatoid arthritis. Asarinin, a natural lignan, has not previously been examined in the context of osteoclast differentiation. Here, we investigated the anti-osteoclastogenic effects of asarinin using RANKL-stimulated RAW264.7 cells. Asarinin significantly suppressed TRAP-positive multinucleated osteoclast formation under the tested conditions. Mechanistically, asarinin selectively inhibited RANKL-induced phosphorylation of p38 and ERK MAPKs, leading to reduced c-Fos expression and inhibition of NFATc1 nuclear translocation. In addition, asarinin disrupted actin ring formation in mature osteoclasts. Collectively, these findings identify asarinin as a pathway-selective inhibitor of osteoclast differentiation, targeting the p38/ERK-c-Fos-NFATc1 axis while sparing parallel signaling pathways.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.