Journal of Oral Tissue Engineering

The Effect of Lysenin on the Differentiation into Osteoclast Cells

Eisuke DOMAE1, Yumiko OGAWA2, Osamu TAKEUCHI3, Yosuke UJII4, Yu KATO5, Toshiya KAWASAKI4, Hiroshi HAYASHI4, Reiko KOMASA6, Naochika DOMAE7, Seiji GODA1 and Takashi IKEO1
1Departments of Biochemistry, 2Departments of Oral and Maxillofacial Surgery, 3Departments of Operative Dentistry, 4Graduate School of Dentistry (Orthodontics), 5Graduate School of Dentistry (Endodontic), 6Graduate School of Dentistry (Operative Dentistry), Osaka Dental University, Osaka, Japan 7Internal Medicine, Osaka Dental University, Osaka, Japan

J Oral Tissue Engin 2011;9(1): 3-9

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.
To investigate the role of lipid rafts in RAW264 cell signaling, lipid rafts were disrupted by depleting cholesterol with lysenin.
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.
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.

Key words:osteoclast, lipid, lysenin, RANKL