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Pristimerin Protects Against OVX-Mediated Bone Loss by Attenuating Osteoclast Formation and Activity via Inhibition of RANKL-Mediated Activation of NF-κB and ERK Signaling Pathways

Authors Li X, Lin X, Wu Z, Su Y, Liang J, Chen R, Yang X, Hou L, Zhao J, Liu Q, Xu F

Received 24 September 2020

Accepted for publication 2 December 2020

Published 7 January 2021 Volume 2021:15 Pages 61—74

DOI https://doi.org/10.2147/DDDT.S283694

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Jianbo Sun


Xuedong Li,1,2,* Xixi Lin,1,2,* Zuoxing Wu,3 Yuangang Su,1,2 Jiamin Liang,1,2 Runfeng Chen,1,2 Xue Yang,1,2 Lei Hou,4 Jinmin Zhao,1,5 Qian Liu,5 Feng Xu1,2,6

1Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 2Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 3School of Medicine, Xiamen University, Xiamen, Fujian 361102, People’s Republic of China; 4Department of Cardiology, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 5Research Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China; 6Department of Subject Planning Shanghai, Ninth People’s Hospital Shanghai, Jiaotong University School of Medicine, Shanghai 200011, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Feng Xu
Department of Subject Planning Shanghai, Ninth People’s Hospital Shanghai, Jiaotong University School of Medicine, Shanghai, People’s Republic of China
Email xufenghhou@163.com
Qian Liu
Research Centre for Regenerative Medicine, Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China
Email luoboqian@hotmail.com

Introduction: Osteoporosis is an osteolytic bone condition characterized by decreased bone strength and increased bone fragility. It is the result of elevated formation or activity of bone-resorbing osteoclasts. Although current therapeutic agents are efficacious against osteoclast-mediated bone loss, detrimental side effects preclude the long-term use of these agents. Pristimerin (PRI) is a naturally occurring quinone-methide triterpenoid that has been revealed to exert anti-inflammatory and anti-tumor effects via regulating various signaling cascades including NF-κB and MAPK activation.
Methods: The bone marrow macrophages were used to confirm the anti-osteoclastic and anti-resorptive functions of PRI in vitro. An in vivo ovariectomy (OVX) model was applied to verify the function of PRI protecting bone loss.
Results: PRI abolished the early activation of NF-κB and ERK MAPK signal cascades thereby thwarting the downstream expression of c-Fos and NFATc1, which prevented the production of mature osteoclasts. In vivo, PRI protects mice against ovariectomy (OVX)-mediated bone loss by diminishing osteoclast formation and bone resorptive activity.
Conclusion: Our study shows that PRI demonstrates therapeutic potential in the effective treatment against osteoclast-induced osteolytic diseases like osteoporosis.

Keywords: osteoporosis, osteoclast, pristimerin, ERK, NF-κB

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