Frontiers in Pharmacology (Mar 2018)
Cepharanthine Prevents Estrogen Deficiency-Induced Bone Loss by Inhibiting Bone Resorption
- Chen-he Zhou,
- Chen-he Zhou,
- Jia-hong Meng,
- Jia-hong Meng,
- Yu-te Yang,
- Yu-te Yang,
- Bin Hu,
- Bin Hu,
- Jian-qiao Hong,
- Jian-qiao Hong,
- Zheng-tao Lv,
- Kun Chen,
- Boon Chin Heng,
- Guang-yao Jiang,
- Guang-yao Jiang,
- Jian Zhu,
- Jian Zhu,
- Zhao-hui Cheng,
- Wei Zhang,
- Wei Zhang,
- Le Cao,
- Le Cao,
- Wei Wang,
- Wei Wang,
- Wei-liang Shen,
- Wei-liang Shen,
- Shi-gui Yan,
- Shi-gui Yan,
- Hao-bo Wu,
- Hao-bo Wu
Affiliations
- Chen-he Zhou
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Chen-he Zhou
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Jia-hong Meng
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jia-hong Meng
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Yu-te Yang
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Yu-te Yang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Bin Hu
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Bin Hu
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Jian-qiao Hong
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jian-qiao Hong
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Zheng-tao Lv
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Kun Chen
- Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Boon Chin Heng
- Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, Hong Kong
- Guang-yao Jiang
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Guang-yao Jiang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Jian Zhu
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Jian Zhu
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Zhao-hui Cheng
- Department of Orthopaedic Surgery, Taizhou First People's Hospital, Taizhou, China
- Wei Zhang
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Wei Zhang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Le Cao
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Le Cao
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Wei Wang
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Wei Wang
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Wei-liang Shen
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Wei-liang Shen
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Shi-gui Yan
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Shi-gui Yan
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- Hao-bo Wu
- Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Hao-bo Wu
- Orthopedic Research Institute of Zhejiang University, Hangzhou, China
- DOI
- https://doi.org/10.3389/fphar.2018.00210
- Journal volume & issue
-
Vol. 9
Abstract
Osteoporosis is a common health problem worldwide caused by an imbalance of bone formation vs. bone resorption. However, current therapeutic approaches aimed at enhancing bone formation or suppressing bone resorption still have some limitations. In this study, we demonstrated for the first time that cepharanthine (CEP, derived from Stephania cepharantha Hayata) exerted a protective effect on estrogen deficiency-induced bone loss. This protective effect was confirmed to be achieved through inhibition of bone resorption in vivo, rather than through enhancement of bone formation in vivo. Furthermore, the in vitro study revealed that CEP attenuated receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast formation, and suppressed bone resorption by impairing the c-Jun N-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathways. The inhibitory effect of CEP could be partly reversed by treatment with anisomycin (a JNK and p38 agonist) and/or SC79 (an AKT agonist) in vitro. Our results thus indicated that CEP could prevent estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis. Hence, CEP might be a novel therapeutic agent for anti-osteoporosis therapy.
Keywords
