title: Dihydroartemisinin, an Anti-Malaria Drug, Suppresses Estrogen Deficiency-Induced Osteoporosis, Osteoclast Formation, and RANKL-Induced Signaling Pathways.
abstract: Osteoporosis is an osteolytic disease that features enhanced osteoclast formation and bone resorption. Identification of agents that can inhibit osteoclast formation and function is important for the treatment of osteoporosis. Dihydroartemisinin is a natural compound used to treat malaria but its role in osteoporosis is not known. Here, we found that dihydroartemisinin can suppress RANKL-induced osteoclastogenesis and bone resorption in a dose-dependent manner. Dihydroartemisinin inhibited the expression of osteoclast marker genes such as cathepsin K, calcitonin receptor, and tartrate-resistant acid phosphatase (TRAcP). Furthermore, dihydroartemisinin inhibited RANKL-induced NF-κB and NFAT activity. In addition, using an in vivo ovariectomized mouse model, we show that dihydroartemisinin is able to reverse the bone loss caused by ovariectomy. Together, this study shows that dihydroartemisinin attenuates bone loss in ovariectomized mice through inhibiting RANKL-induced osteoclast formation and function. This indicates that dihydroartemisinin, the first physiology or medicine nobel prize discovery of China, is a potential treatment option against osteolytic bone disease. © 2015 American Society for Bone and Mineral Research.
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.|Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Mingli
authors.initials: M
authors.lastname: Yang
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.|Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.|Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Cheng
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Xixi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tickner
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.|Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D002478:Cells, Cultured; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D051379:Mice; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010024:Osteoporosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004967:Estrogens; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C039060:artenimol
keywords: BONE RESORPTION; DIHYDROARTEMISININ; OSTEOCLAST; OSTEOLYSIS; RANKL