Galectin-9 induces osteoblast differentiation through the CD44/Smad signaling pathway.
Galectin-9 is a beta-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.
Tanikawa
Rena
R
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Tanikawa
Takahisa
T
Hirashima
Mitsuomi
M
Yamauchi
Akira
A
Tanaka
Yoshiya
Y
D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D037161:Galectins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D051785:Smad Proteins / Q000378:metabolism*; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D051904:Smad8 Protein / Q000378:metabolism
D019485:Bone Morphogenetic Proteins; C497483:CD44 protein, human; D037161:Galectins; D018960:Hyaluronan Receptors; C105032:LGALS9 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D052004:Bone Morphogenetic Protein Receptors