Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis

Cong Jin; Jiewen Zheng; Qichang Yang; Yewei Jia; Haibo Li; Xuewen Liu; Yangjun Xu; Zhuolin Chen; Lei He

doi:10.2174/0113862073252310230925062415

Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis

Comb Chem High Throughput Screen. 2023 Oct 2. doi: 10.2174/0113862073252310230925062415. Online ahead of print.

Authors

Cong Jin¹, Jiewen Zheng^{1

2}, Qichang Yang^{1

3}, Yewei Jia¹, Haibo Li¹, Xuewen Liu^{3

1}, Yangjun Xu^{2

1}, Zhuolin Chen^{4

1}, Lei He¹

Affiliations

¹ Department of Orthopaedics, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, Zhejiang 312000, China.
² Shaoxing University School of Medicine, Shaoxing, Zhejiang 312000, China.
³ The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
⁴ Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, China.

PMID: 37807416
DOI: 10.2174/0113862073252310230925062415

Abstract

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.

Keywords: Moraceae; Morusin; Postmenopausal osteoporosis; RANKL; osteoclastogenesis; osteoclasts.