Lycorine suppresses RANKL-induced osteoclastogenesis in vitro and prevents ovariectomy-induced osteoporosis and titanium particle-induced osteolysis in vivo

Sci Rep. 2015 Aug 4:5:12853. doi: 10.1038/srep12853.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amaryllidaceae Alkaloids / pharmacology*
  • Animals
  • Bone Density Conservation Agents / pharmacology*
  • Bone Marrow / drug effects
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Kinase 7 / genetics
  • MAP Kinase Kinase 7 / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteogenesis / drug effects*
  • Osteolysis / chemically induced
  • Osteolysis / genetics
  • Osteolysis / pathology
  • Osteolysis / prevention & control*
  • Osteoporosis / genetics
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Osteoporosis / prevention & control*
  • Ovariectomy
  • Phenanthridines / pharmacology*
  • Primary Cell Culture
  • RANK Ligand / antagonists & inhibitors
  • RANK Ligand / genetics*
  • RANK Ligand / metabolism
  • Signal Transduction
  • Titanium

Substances

  • Amaryllidaceae Alkaloids
  • Bone Density Conservation Agents
  • Phenanthridines
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Titanium
  • MAP Kinase Kinase 4
  • MAP Kinase Kinase 7
  • Map2k7 protein, mouse
  • lycorine