Actin binding LIM 1 (abLIM1) negatively controls osteoclastogenesis by regulating cell migration and fusion
Actin binding LIM 1 (abLIM1) negatively controls osteoclastogenesis by regulating cell migration and fusion
复制标题
DOI：
10.1002/jcp.26605
复制
发表时间：
2019-01-01
影响因子：
5.6
通讯作者：
Tsukuba, Takayuki
中科院分区：
文献类型：
--
作者：
Narahara, Haruna;Sakai, Eiko;Tsukuba, Takayuki
肌动蛋白结合 LIM 1 (abLIM1) 是一种细胞骨架肌动蛋白结合蛋白，与肌动蛋白丝和细胞质靶标之间的相互作用有关。先前的生化和细胞化学研究表明 abLIM1 与视网膜和肌肉中的 F-肌动蛋白相互作用并共定位。然而，abLIM1是否调节破骨细胞分化尚未阐明。在这项研究中，我们研究了 abLIM1 在破骨细胞分化和功能中的作用。我们发现 abLIM1 表达在核因子 kappa-B 配体受体激活剂 (RANKL) 诱导的破骨细胞分化过程中上调，并且 abLIM1 的新转录物仅在破骨细胞中表达。在小鼠单核细胞系 RAW-D 中过度表达 abLIM1 会抑制破骨细胞分化，并降低一些破骨细胞标记基因的表达。相比之下，小干扰RNA诱导的abLIM1敲除增强了多核破骨细胞的形成，并显着增加了破骨细胞标记基因的表达。从机制上讲，abLIM1 调节微管蛋白在破骨细胞中的定位、迁移和融合。因此，这些结果表明 abLIM1 通过调节肌动蛋白形成介导的细胞迁移和融合来负向控制破骨细胞分化。
Actin binding LIM 1 (abLIM1) is a cytoskeletal actin-binding protein that has been implicated in interactions between actin filaments and cytoplasmic targets. Previous biochemical and cytochemical studies have shown that abLIM1 interacts and co-localizes with F-actin in the retina and muscle. However, whether abLIM1 regulates osteoclast differentiation has not yet been elucidated. In this study, we examined the role of abLIM1 in osteoclast differentiation and function. We found that abLIM1 expression was upregulated during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation, and that a novel transcript of abLIM1 was exclusively expressed in osteoclasts. Overexpression of abLIM1 in the murine monocytic cell line, RAW-D suppressed osteoclast differentiation and decreased expression of several osteoclast-marker genes. By contrast, small interfering RNA-induced knockdown of abLIM1 enhanced the formation of multinucleated osteoclasts and markedly increased the expression of the osteoclast-marker genes. Mechanistically, abLIM1 regulated the localization of tubulin, migration, and fusion in osteoclasts. Thus, these results indicate that abLIM1 negatively controls osteoclast differentiation by regulating cell migration and fusion mediated via actin formation.