|発表タイトル||Suppression of osteoclastogenesis by Lysenin: a sphingomyelin specific toxin by modulating RANK signaling pathways|
|学会名||The 4th Sino-Japanese Conference on Stomatology 2008|
|発表者・共同発表者||Goda S, Domae E, Ogawa Y, Takeuchi S, Yoshikado R, Sakata T, Yoshikawa Y, Tamura I, Kamada A, Yamamoto K, Morita S, Ikeo T|
|学会抄録||「Program & Abstracts of the Sino-Japanese Conference on Stomatology 2008」 pp.94
「Program & Abstracts of the Sino-Japanese Conference on Stomatology 2008」 pp.94
|概要||Objectives: Sphingomyelin (SM) is a major component of lipid rafts, which are specialized structures that enhance the efficiency of membrane receptor signaling and are the main source of ceramide. Among lipid rafts made up of cholesterol, glycosphingolipids, and sphingomyelin (SM)-rich membrane microdomains, receptor activator of NF-kappaB (RANK) is facilitated by the localization of receptors and proximal signaling components. Rafts are involved in receptor activator of NF-kappaB ligand (RANKL )/RANK-induced differentiation into osteoclasts through the translocation and clustering of RANK into rafts upon stimulation. Lysenin, an SM-directed cytolysin isolated from the earthworm, binds to sphingomyelin-rich membrane domains and induces pore formation in the plasma membrane. We examined that the role of SM in RANKL-stimulated proliferation and differentiation into osteoclasts with RAW264 cells.
Methodology and Results: Lysenin did not affect proliferation in RAW264 cells incubated with 100 ng /ml lysenin in 7.5 % FBS for 24 h. In contrast, in RAW264 cells incubated with 50 ng/ml RANKL in the presence or absence of lysenin for 5 days in 7.5% FBSα-MEM and analyzed by tartrate-resistant acid phosphatase (TRAP) staining, RANKL-mediated differentiation was markedly inhibited by lysenin in a dose-dependent manner. RANKL-mediated phosphorylation of MAP kinase, p38 and MEK, was blocked by 100 ng/ml lysenin.
Conclusion: These results suggest that RANKL/RANK can initiate lipid raft micro domain-dependent signaling events that affect the differentiation and phosphorylation of MAP kinase.