Premium
Interaction of Galectin‐9 With Lipid Rafts Induces Osteoblast Proliferation Through the c‐Src/ERK Signaling Pathway
Author(s) -
Tanikawa Rena,
Tanikawa Takahisa,
Okada Yosuke,
Nakano Kazuhisa,
Hirashima Mitsuomi,
Yamauchi Akira,
Hosokawa Ryuji,
Tanaka Yoshiya
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.071008
Subject(s) - lipid raft , phosphorylation , microbiology and biotechnology , ganglioside , osteoblast , proto oncogene tyrosine protein kinase src , galectin , cholera toxin , mapk/erk pathway , signal transduction , chemistry , biology , biochemistry , endocrinology , in vitro
Galectin‐9 is a β‐galactoside‐binding lectin expressed in various tissues, including bone. The role of galectin‐9 in human osteoblasts, however, remains unclear. This study showed that galectin‐9 interacts with lipid rafts and induces osteoblast proliferation through the c‐Src/ERK signaling pathway. Introduction: Galectin‐9 is a β‐galactoside‐binding lectin that modulates many biological functions by interacting with particular carbohydrates attached to proteins and lipids. However, the role of galectin‐9 in bone metabolism and osteoblast proliferation remains unclear. This study investigated the effects of galectin‐9 on osteoblast proliferation and its signaling mechanisms. Materials and Methods: The effect of galectin‐9 on osteoblast proliferation was tested by measuring the conversion of tetrazolium salt WST‐8 to formazan. Protein phosphorylation was assayed by western blotting and confocal microscopy was used to localize lipid rafts. Results: Galectin‐9–induced proliferation of the obtained osteoblasts in a dose‐dependent manner, whereas galectin‐1, ‐3, and ‐4 did not. Galectin‐9–induced phosphorylation of c‐Src and subsequent ERK1/ERK2 in the osteoblasts. The galectin‐9–induced phosphorylation and proliferation were inhibited by PP2, a selective inhibitor of c‐Src. Galectin‐9–induced clustering of lipid rafts detected by cholera toxin B (CTB; binding the raft‐resident ganglioside GM1) using confocal microscopy. Cross‐linking of the GM1 ganglioside with CTB by anti‐CTB antibody‐induced phosphorylation of c‐Src, whereas disruption of galectin‐9–induced lipid rafts by β‐methylcyclodextrin reduced c‐Src phosphorylation and proliferation of the cells. Conclusions: These results suggest that galectin‐9, but not other galectins, induced proliferation of human osteoblasts through clustering lipid rafts on membrane and subsequent phosphorylation of the c‐Src/ERK signaling pathway.