Li Yin-Ji, Kukita Akiko, Teramachi Junpei, Nagata Kengo, Wu Zhou, Akamine Akifumi, Kukita Toshio
Department of Hard Tissue Regeneration Control and Science, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Lab Invest. 2009 Jan;89(1):26-37. doi: 10.1038/labinvest.2008.111. Epub 2008 Nov 17.
Galectin-3 is a beta-galactoside-binding animal lectin having pleiotropic effects on cell growth, differentiation, and apoptosis. This lectin has been shown to be involved in phagocytosis by macrophages and in inflammation. Here we investigated an involvement of galectin-3 in the regulatory process of inflammatory bone resorption in rats with adjuvant-induced arthritis (AA rats) accompanying severe bone destruction in the ankle joints. The protein level of galectin-3 in the ankle-joint extracts was markedly augmented at week 3 after adjuvant injection, at the time when severe bone destruction was observed. Immunohistochemical analysis revealed an extremely high expression of galectin-3 in macrophages and granulocytes infiltrated in the area of severe bone destruction. To estimate the role of galectin-3 in osteoclastogenesis and osteoclastic bone resorption, recombinant galectin-3 was added to in vitro culture systems. Galectin-3 markedly inhibited the formation of osteoclasts in cultures of murine osteoclast precursor cell line as well as in rat bone marrow culture systems. This inhibition was not observed by heat-inactivated galectin-3 or by galectin-7. Although recombinant galectin-3 did not affect signaling through mitogen-activated protein kinase (MAPK) or nuclear factor-kappaB (NF-kappaB), it specifically suppressed the induction of nuclear factor of activated T-cells c1 (NFATc1). Galectin-3 significantly inhibited dentine resorption by mature osteoclasts in vitro. Furthermore, in vivo studies clearly showed a significant suppression of bone destruction and osteoclast recruitment accompanying arthritis, when galectin-3 was injected into the cavity of ankle joint of AA rats. Thus, abundant galectin-3 observed in the area of severe bone destruction may act as a negative regulator for the upregulated osteoclastogenesis accompanying inflammation to prevent excess bone destruction.
半乳糖凝集素-3是一种结合β-半乳糖苷的动物凝集素，对细胞生长、分化和凋亡具有多效性作用。已证明这种凝集素参与巨噬细胞的吞噬作用和炎症反应。在此，我们研究了半乳糖凝集素-3在佐剂性关节炎大鼠（AA大鼠）炎症性骨吸收的调节过程中的作用，该大鼠伴有踝关节严重骨破坏。在佐剂注射后第3周，即观察到严重骨破坏时，踝关节提取物中半乳糖凝集素-3的蛋白水平显著升高。免疫组织化学分析显示，在严重骨破坏区域浸润的巨噬细胞和粒细胞中，半乳糖凝集素-3表达极高。为了评估半乳糖凝集素-3在破骨细胞生成和破骨细胞性骨吸收中的作用，将重组半乳糖凝集素-3添加到体外培养系统中。半乳糖凝集素-3显著抑制小鼠破骨细胞前体细胞系培养物以及大鼠骨髓培养系统中破骨细胞的形成。热灭活的半乳糖凝集素-3或半乳糖凝集素-7未观察到这种抑制作用。尽管重组半乳糖凝集素-3不影响丝裂原活化蛋白激酶（MAPK）或核因子-κB（NF-κB）信号通路，但它特异性抑制活化T细胞核因子c1（NFATc1）的诱导。半乳糖凝集素-3在体外显著抑制成熟破骨细胞对牙本质的吸收。此外，体内研究清楚地表明，当将半乳糖凝集素-3注射到AA大鼠的踝关节腔中时，可显著抑制伴随关节炎的骨破坏和破骨细胞募集。因此，在严重骨破坏区域观察到的大量半乳糖凝集素-3可能作为炎症伴随的破骨细胞生成上调的负调节因子，以防止过度的骨破坏。
