Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis

Background: Postmenopausal osteoporosis (PMOP) is a classic type of osteoporosis that has gradually become a significant health problem worldwide. There is an urgent need for a safe alternative therapeutic agent considering the poor therapeutic strategies currently available for this disease. The roots and bark of the Morus australis tree (Moraceae) are used to make a traditional Chinese medicine known as "Morusin", and accumulating evidence has demonstrated its multiple activities, such as anti-inflammatory and anti-tumor effects. Objective: In this study, we aim to explore the effect of Morusin on mouse osteoclasts and its mechanism. Methods: In this study, we explored the inhibitory effects of Morusin on murine osteoclasts in vitro and its mechanism, and the protective effect of Morusin on an ovariectomy (OVX)-induced osteoporosis model in vivo. Results: The results showed that Morusin prevented OVX-induced bone loss and dramatically decreased RANKL-induced osteoclastogenesis. Morusin interfered with RANKL-activated NF- ΚB, MAPK, and PI3K/AKT signaling pathways. The expression of three master factors that control osteoclast differentiation, c-Fos, NFATc1, and c-Jun, was reduced by Morusin treatment. Collectively, in vitro results indicated that Morusin has a protective effect on OVX-induced bone loss in a mouse model. Conclusion: Our data provide encouraging evidence that Morusin may be an effective treatment for PMOP.