title: Lycorine suppresses RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced osteoporosis and titanium particle-induced osteolysis in vivo.
abstract: Osteoclasts play an important role in diseases involving bone loss. In this study, we assessed the effect of a plant-derived natural alkaloid (lycorine, or LY) on osteoclastogenesis in vitro and in vivo. Our in vitro study showed that receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis could be inhibited by LY; this effect was due to inhibition of mitogen-activated protein kinase (MAPK) signalling via MAP kinase kinases (MKKs). The MAPK agonist anisomycin could partially rescue the inhibitory effect of LY. Furthermore, LY also played a protective role in both a murine ovariectomy (OVX)-induced osteoporosis model and a titanium particle-induced osteolysis model. These results confirmed that LY was effective in preventing osteoclast-related diseases in vivo. In conclusion, our results show that LY is effective in suppressing osteoclastogenesis and therefore could be used to treat OVX-induced osteoporosis and wear particle-induced osteolysis.
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Department of Bone and Soft Tissue Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Gu
authors.initials: G
authors.lastname: Jin
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Kang-Mao
authors.initials: KM
authors.lastname: Huang
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Ma
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Xiao-Zhen
authors.initials: XZ
authors.lastname: Tang
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Zhou
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Hu
authors.affiliation: Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China.
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.affiliation: 1] Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China [2] Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou 310016, China.
authors.forename: Shun-Wu
authors.initials: SW
authors.lastname: Fan
mesh_terms: D047151:Amaryllidaceae Alkaloids / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D048688:MAP Kinase Kinase 7 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D010024:Osteoporosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010052:Ovariectomy; D010617:Phenanthridines / Q000494:pharmacology*; D061251:Primary Cell Culture; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014025:Titanium
chemical_list: D047151:Amaryllidaceae Alkaloids; D050071:Bone Density Conservation Agents; D010617:Phenanthridines; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D014025:Titanium; D048670:MAP Kinase Kinase 4; D048688:MAP Kinase Kinase 7; C482570:Map2k7 protein, mouse; C015330:lycorine