Pristimerin Suppresses RANKL-Induced Osteoclastogenesis and Ameliorates Ovariectomy-Induced Bone Loss

Dahu Qi; Hui Liu; Xuying Sun; Danni Luo; Meipeng Zhu; Tenghui Tao; Chenghao Gao; Chuankun Zhou; Wei Zhou; Jun Xiao

doi:10.3389/fphar.2020.621110

Pristimerin Suppresses RANKL-Induced Osteoclastogenesis and Ameliorates Ovariectomy-Induced Bone Loss

Front Pharmacol. 2021 Jan 15:11:621110. doi: 10.3389/fphar.2020.621110. eCollection 2020.

Authors

Dahu Qi¹, Hui Liu^{1

2}, Xuying Sun¹, Danni Luo¹, Meipeng Zhu¹, Tenghui Tao¹, Chenghao Gao¹, Chuankun Zhou¹, Wei Zhou³, Jun Xiao¹

Affiliations

¹ Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, China.
³ Institute of Hepatobiliary Diseases, Transplant Center, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, China.

Abstract

Osteoporosis is characterized by bone loss and destruction of trabecular architecture, which greatly increases the burden on the healthcare system. Excessive activation of osteoclasts is an important cause of osteoporosis, and suppression of osteoclastogenesis is helpful for the treatment of osteoporosis. Pristimerin, a natural compound, possesses numerous pharmacological effects via inactivating the NF-κB and MAPK pathways, which are closely related to osteoclastogenesis process. However, the relationship between Pristimerin and osteoclastogenesis requires further investigation. In this research, we examined the effect of Pristimerin on osteoclastogenesis and investigated the related mechanisms. Our results showed Pristimerin inhibited RANKL-induced osteoclast differentiation and osteoclastic bone resorption in vitro, with decreased expression of osteoclastogenesis-related markers including c-Fos, NFATc1, TRAP, Cathepsin K, and MMP-9 at both mRNA and protein levels. Furthermore, Pristimerin suppressed NF-κB and MAPK signaling pathways, reduced reactive oxygen species (ROS) production and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling during osteoclastogenesis. Our in vivo experiments showed that Pristimerin remarkably ameliorated ovariectomy-induced bone loss, reduced serum levels of TNF-α, IL-1β, IL-6, and RANKL, and increased serum level of osteoprotegerin (OPG). Therefore, our research indicated that Pristimerin is a potential chemical for the treatment of osteoporosis.

Keywords: MAPK; NF-κB; Nrf2; osteoclastogenesis; pristimerin.