title: Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways.
abstract: 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.
authors.affiliation: Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. liulianwang@hotmail.com.|Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. liulianwang@hotmail.com.|Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. liulianwang@hotmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. luoboqian@hotmail.com.|Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. luoboqian@hotmail.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Pathology and Laboratory Medicine, the University of Western Australia, Perth WA 6009, Australia. 20463692@student.uwa.edu.au.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: School of Pathology and Laboratory Medicine, the University of Western Australia, Perth WA 6009, Australia. jinbo.yuan@research.uwa.edu.au.
authors.forename: Jin Bo
authors.initials: JB
authors.lastname: Yuan
authors.affiliation: Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. sisic_082531@hotmail.com.|Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. sisic_082531@hotmail.com.
authors.forename: Xixi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. 15877171979@163.com.|Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. 15877171979@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Zeng
authors.affiliation: Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. lxn120@126.com.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Liang
authors.affiliation: Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. zhaojingmin@126.com.|Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. zhaojingmin@126.com.|Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. zhaojingmin@126.com.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. jiake.xu@uwa.edu.au.|Department of Orthopedics Surgery, the First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China. jiake.xu@uwa.edu.au.|School of Pathology and Laboratory Medicine, the University of Western Australia, Perth WA 6009, Australia. jiake.xu@uwa.edu.au.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004224:Diterpenes / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy / Q000009:adverse effects*; D010766:Phosphorylation; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D004224:Diterpenes; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; C030419:andrographolide; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: OVX; RANKL; andrographolide; bone loss; osteoclastogenesis