title: Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction.
abstract: Galectins are a unique family of lectins bearing one or two carbohydrate recognition domains (CRDs) that have the ability to bind molecules with β-galactoside-containing carbohydrates. It has been shown that galectins regulate not only cell growth and differentiation but also immune responses, as well as inflammation. Galectin-9, a tandem repeat type of galectin, was originally identified as a chemotactic factor for eosinophils, and is also involved in the regulatory process of inflammation. Here, we examined the involvement of galectin-9 and its receptor, T-cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3), in the control of osteoclastogenesis and inflammatory bone destruction. Expression of Tim-3 was detected in osteoclasts and its mononuclear precursors in vivo and in vitro. Galectin-9 markedly inhibited osteoclastogenesis as evaluated in osteoclast precursor cell line RAW-D cells and primary bone marrow cells of mice and rats. The inhibitory effects of galectin-9 on osteoclastogenesis was negated by the addition of β-lactose, an antagonist for galectin binding, suggesting that the inhibitory effect of galectin-9 was mediated through CRD. When galectin-9 was injected into rats with adjuvant-induced arthritis, marked suppression of bone destruction was observed. Inflammatory bone destruction could be efficiently ameliorated by controlling the Tim-3/galectin-9 system in rheumatoid arthritis.
authors.affiliation: 1] Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan [2] Department of Orthodontics, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Moriyama
authors.affiliation: Department of Microbiology, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kukita
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Yin-Ji
authors.initials: YJ
authors.lastname: Li
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Uehara
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Jing-Qi
authors.initials: JQ
authors.lastname: Zhang
authors.affiliation: Department of Orthodontics, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takahashi
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Faculty of Dental Sciences, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kukita
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D001862:Bone Resorption / Q000209:etiology* / Q000378:metabolism; D005260:Female; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D007785:Lactose; D008297:Male; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D037161:Galectins; C569429:Havcr2 protein, rat; D011956:Receptors, Cell Surface; C513912:galectin 9, rat; D007785:Lactose