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A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
Published on: March 15, 2018
Asarinin Inhibits RANKL-Induced Osteoclast Differentiation by Targeting the p38/ERK-c-Fos-NFATc1 Axis
Lifang Zhang1,2, Chengxu Xie1,2, Xinyi Bao1,2
1Osteoimmunology & Drug Discovery Research Group, Department of Biology, College of Science, Mathematics and Technology, Wenzhou-Kean University, 88 Daxue Road, Wenzhou 325060, China.
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. Mechanistically, asarinin selectively inhibited RANKL-induced phosphorylation of p38 and ERK MAPKs, leading to reduced c-Fos expression and inhibition of NFATc1 activation. In addition, asarinin disrupted actin ring formation in mature osteoclasts. Collectively, these findings identify asarinin as a pathway-selective inhibitor of osteoclast differentiation, acting through a mechanism consistent with modulation of the p38/ERK-c-Fos-NFATc1 signaling cascade while sparing parallel signaling pathways.
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