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Galectin-9 induces osteoblast differentiation through the CD44/Smad signaling pathway
Authors:Rena Tanikawa  Mitsuomi Hirashima  Yoshiya Tanaka
Institution:a First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
b Department of Cell Regulation, School of Medicine, Kagawa University, Kagawa, Japan
c Department of Immunology and Immunopathology, School of Medicine, Kagawa University, Kagawa, Japan
Abstract:Galectin-9 is a β-galactoside-binding lectin expressed in various tissues. It binds various glycoconjugates and modulates a variety of biological functions in various cell types. Although galectin-9 is expressed in bone, its function in human osteoblasts remains unclear. We demonstrate that galectin-9 induces osteoblast differentiation through the CD44/Smad signaling pathway in the absence of bone morphogenetic proteins (BMPs). Galectin-9 increases alkaline phosphatase activities in human osteoblasts and induces the phosphorylation of Smad1/5/8 and translocation of Smad4 to the nucleus in the absence of BMPs. Galectin-9 also induces binding of Smad4 to the Id1 promoter and increases its activity. Anti-CD44 antibody inhibits Smad1/5/8 phosphorylation by galectin-9. Galectin-9 binds to CD44 and induces the formation of a CD44/BMP receptor complex. Because Smad1 is phosphorylated by BMP receptors, we propose that formation of the CD44/BMP receptor complex induced by galectin-9 may provide a trigger for the activation of Smads.
Keywords:Galectin-9  Osteoblast  CD44  Smad
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