The Effect of Lysenin on the Differentiation into Osteoclast Cells

DOI
  • DOMAE Eisuke
    Departments of Biochemistry, Osaka Dental University, Osaka, Japan
  • OGAWA Yumiko
    Departments of Oral and Maxillofacial Surgery, Osaka Dental University, Osaka, Japan
  • TAKEUCHI Osamu
    Departments of Operative Dentistry, Osaka Dental University, Osaka, Japan
  • UJII Yosuke
    Graduate School of Dentistry (Orthodontics), Osaka Dental University, Osaka, Japan
  • KATO Yu
    Graduate School of Dentistry (Endodontic), Osaka Dental University, Osaka, Japan
  • KAWASAKI Toshiya
    Graduate School of Dentistry (Orthodontics), Osaka Dental University, Osaka, Japan
  • HAYASHI Hiroshi
    Graduate School of Dentistry (Orthodontics), Osaka Dental University, Osaka, Japan
  • KOMASA Reiko
    Graduate School of Dentistry (Operative Dentistry), Osaka Dental University, Osaka, Japan
  • DOMAE Naochika
    Internal Medicine, Osaka Dental University, Osaka, Japan
  • GODA Seiji
    Departments of Biochemistry, Osaka Dental University, Osaka, Japan
  • IKEO Takashi
    Departments of Biochemistry, Osaka Dental University, Osaka, Japan

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抄録

Bone is continuously remodeled by bone resorption and formation. The bone metabolism is tightly regulated to maintain homeostasis. Deviation from the normal conditions of bone resorption would result in bone diseases. Lipid rafts are specialized plasma membrane microdomains enriched with glycosphingolipids, sphingomyelin and cholesterol. Lipid rafts are important for the transport of selected membranes and relay stations in intracellular signaling.<br>To investigate the role of lipid rafts in RAW264 cell signaling, lipid rafts were disrupted by depleting cholesterol with lysenin.<br>We found that RANKL-induced differentiation into osteoclasts was markedly inhibited by lysenin in a dose-dependent manner. Lysenin abolished RANKL-induced phosphorylation of PLCγ2, Gab2, AKT, ERK1/2, p38.<br>These data suggest that a crucial role for cholesterol in the regulation of the RANKL-mediated signaling pathway and osteoclast differentiation in RAW264 cells, which reflects its importance in the formation of plasma membrane lipid rafts.

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