title: Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo.
abstract: Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases.
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.|Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, China.|Collaborative Innovation Center of Guangxi Biological Medicine, Guangxi Medical University, Nanning, China.
authors.forename: Cheng-Ming
authors.identifier: http://orcid.org/0000-0002-4361-6863
authors.initials: CM
authors.lastname: Wei
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.|Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Fang-Ming
authors.initials: FM
authors.lastname: Song
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.
authors.forename: Xi-Xi
authors.initials: XX
authors.lastname: Lin
authors.affiliation: Collaborative Innovation Center of Guangxi Biological Medicine, Guangxi Medical University, Nanning, China.|Rehabilitation Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, China.
authors.forename: Yi-Ji
authors.initials: YJ
authors.lastname: Su
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.|School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Spine Surgery, Department of Orthopedics, Research Center of Spinal and Pelvic Tumor, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.|Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, China.|Collaborative Innovation Center of Guangxi Biological Medicine, Guangxi Medical University, Nanning, China.
authors.forename: Shao-Hui
authors.initials: SH
authors.lastname: Zong
authors.affiliation: Research Centre for Regenerative Medicine and Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China.|Orthopaedic Department, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Guangxi, China.|Collaborative Innovation Center of Guangxi Biological Medicine, Guangxi Medical University, Nanning, China.
authors.forename: Jin-Min
authors.initials: JM
authors.lastname: Zhao
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D001862:Bone Resorption / Q000188:drug therapy* / Q000235:genetics; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation; D059748:Proteolysis; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D037621:Artemisinins; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D053245:RANK Ligand; C498144:Rela protein, mouse; C505689:Tnfsf11 protein, mouse; D051996:Transcription Factor RelA; D000077332:Artesunate
keywords: Artesunate; lytic bone diseases; osteoclast; osteoclastogenesis