Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways

International Journal of Molecular Sciences

Tao Wang³  Qian Liu³  Lin Zhou²  Jin Bo Yuan²  Xixi Lin³  Rong Zeng³  Xiaonan Liang¹  Jinmin Zhao³  Jiake Xu³ 

[1] Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China;School of Pathology and Laboratory Medicine, the University of Western Australia, Perth WA 6009, Australia;Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China;

关键词: andrographolide;    osteoclastogenesis;    RANKL;    OVX;    bone loss;   

DOI  :  10.3390/ijms161126039

来源: mdpi

【 摘 要 】

Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX) mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT). Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk), TRACP (Acp5), and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.