A possible suppressive role of galectin-3 in upregulated osteoclastogenesis accompanying adjuvant-induced arthritis in rats
A possible suppressive role of galectin-3 in upregulated osteoclastogenesis accompanying adjuvant-induced arthritis in rats
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DOI：
10.1038/labinvest.2008.111
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发表时间：
2009-01-01
影响因子：
5
通讯作者：
Kukita, Toshio
中科院分区：
文献类型：
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作者：
Li, Yin-Ji;Kukita, Akiko;Kukita, Toshio
半乳糖凝集素-3是一种β-半乳糖苷结合的动物凝集素，对细胞生长、分化和凋亡具有多效性作用。这种凝集素已被证明参与巨噬细胞的吞噬作用和炎症。在这里，我们研究了半乳糖凝集素-3在炎症性骨吸收的调节过程中的参与，在大鼠炎症性关节炎（AA大鼠）伴随着严重的骨破坏在踝关节。在佐剂注射后第3周，在观察到严重骨破坏时，踝关节提取物中的半乳糖凝集素-3的蛋白水平显著增加。免疫组化分析显示，在严重骨质破坏的区域中，巨噬细胞和粒细胞浸润中半乳糖凝集素-3的表达极高。为了评估半乳糖凝集素-3在破骨细胞生成和骨吸收中的作用，将重组半乳糖凝集素-3加入体外培养系统中。半乳糖凝集素-3显着抑制小鼠破骨细胞前体细胞系以及大鼠骨髓培养系统中的破骨细胞的形成。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不影响通过丝裂原活化蛋白激酶（MAPK）或核因子-κ B（NF-κ B）的信号传导，但其特异性抑制活化T细胞核因子c1（NFATc 1）的诱导。Galectin-3在体外能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，伴随关节炎的骨破坏和破骨细胞募集受到显著抑制。因此，在严重骨破坏区域中观察到的丰富的半乳糖凝集素-3可以作为伴随炎症的破骨细胞生成上调的负调节剂，以防止过度的骨破坏。
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-kappa B (NF-kappa B), 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.