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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amaryllidaceae Alkaloids / pharmacology*
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Animals
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Bone Density Conservation Agents / pharmacology*
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Bone Marrow / drug effects
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Cell Differentiation / drug effects
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Cell Survival / drug effects
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Disease Models, Animal
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Female
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Gene Expression Regulation
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MAP Kinase Kinase 4 / genetics
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MAP Kinase Kinase 4 / metabolism
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MAP Kinase Kinase 7 / genetics
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MAP Kinase Kinase 7 / metabolism
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Macrophages / drug effects
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Macrophages / metabolism
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Macrophages / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Osteoclasts / drug effects
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Osteoclasts / metabolism
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Osteoclasts / pathology
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Osteogenesis / drug effects*
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Osteolysis / chemically induced
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Osteolysis / genetics
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Osteolysis / pathology
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Osteolysis / prevention & control*
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Osteoporosis / genetics
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Osteoporosis / metabolism
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Osteoporosis / pathology
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Osteoporosis / prevention & control*
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Ovariectomy
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Phenanthridines / pharmacology*
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Primary Cell Culture
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RANK Ligand / antagonists & inhibitors
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RANK Ligand / genetics*
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RANK Ligand / metabolism
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Signal Transduction
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Titanium
Substances
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Amaryllidaceae Alkaloids
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Bone Density Conservation Agents
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Phenanthridines
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RANK Ligand
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Tnfsf11 protein, mouse
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Titanium
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MAP Kinase Kinase 4
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MAP Kinase Kinase 7
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Map2k7 protein, mouse
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lycorine