TY - JOUR
T1 - Regulation of osteoclastogenesis through Tim-3
T2 - Possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction
AU - Moriyama, Kanako
AU - Kukita, Akiko
AU - Li, Yin Ji
AU - Uehara, Norihisa
AU - Zhang, Jing Qi
AU - Takahashi, Ichiro
AU - Kukita, Toshio
N1 - Funding Information:
We thank Dr Yasuyoshi Osaki, Dr Takayoshi Yamaza, Dr Tomoko Kitsuki and Dr Mizuho Kido of Kyushu University, Faculty of Dental Science for helpful suggestions. This work is funded in part by a Grant-in-Aid for Scientific Research (B) and (Challenging Exploratory Research) of Japan Society for Promotion of Science (JSPS) (project nos. 21390492, 21659424, 23659860, 25670780, and 26670803).
Publisher Copyright:
© 2014 USCAP, Inc All rights reserved.
PY - 2014/11/5
Y1 - 2014/11/5
N2 - 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.
AB - 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.
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U2 - 10.1038/labinvest.2014.107
DO - 10.1038/labinvest.2014.107
M3 - Article
C2 - 25264706
AN - SCOPUS:84908473593
VL - 94
SP - 1200
EP - 1211
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 11
ER -