Regulation of osteoclastogenesis through Tim-3: possible involvement of the Tim-3/galectin-9 system in the modulation of inflammatory bone destruction

• Published in: Laboratory investigation Vol. 94; no. 11; pp. 1200 - 1211
• Main Authors: Moriyama, Kanako, Kukita, Akiko, Li, Yin-Ji, Uehara, Norihisa, Zhang, Jing-Qi, Takahashi, Ichiro, Kukita, Toshio
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2014; Nature Publishing Group
• Subjects: 631/250/249/1313/498; 631/250/256; 631/80/86; Animals; Arthritis - chemically induced; Arthritis - complications; Arthritis - metabolism; Bone Resorption - etiology; Bone Resorption - metabolism; Female; Galectins - metabolism; Humans; Laboratory Medicine; Lactose; Male; Medicine; Medicine & Public Health; Mice, Inbred C57BL; Osteoclasts - physiology; Pathology; Rats, Sprague-Dawley; Receptors, Cell Surface - metabolism; research-article
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2014.107

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.