The Effect of Lysenin on the Differentiation into Osteoclast Cells

Abstract

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.