The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts
The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts
复制标题
DOI：
10.1007/s00774-015-0683-1
复制
发表时间：
2016-07
影响因子：
3.3
通讯作者：
Gnanasagar J. Thirukonda;Shunsuke Uehara;Takahiro Nakayama;T. Yamashita;Yukio Nakamura;T. Mizoguchi;N. Takahashi;K. Yagami;N. Udagawa;Yasuhiro Kobayashi
中科院分区：
文献类型：
--
作者：
Gnanasagar J. Thirukonda;Shunsuke Uehara;Takahiro Nakayama;T. Yamashita;Yukio Nakamura;T. Mizoguchi;N. Takahashi;K. Yagami;N. Udagawa;Yasuhiro Kobayashi
破骨细胞的细胞骨架组织是骨吸收所必需的。以前认为肌动蛋白细胞骨架的组织化需要发动蛋白与三磷酸鸟苷（GTP）的结合。然而，在肌动蛋白细胞骨架的组织以及在破骨细胞的骨吸收活性的GTdR活性的作用仍然不清楚。本研究探讨了dynasore（dynamin的GT3活性抑制剂）在体外和体内对小鼠破骨细胞骨吸收活性和肌动蛋白环形成的影响。Dynasore通过抑制肌动蛋白环的形成和快速破坏破骨细胞中的肌动蛋白环来抑制破骨细胞培养物中吸收陷窝的形成。延时图像分析显示，dynasore在30分钟内使破骨细胞中的肌动蛋白环收缩。Dynasore腹腔内给药可抑制核因子κB配体受体激活剂（RANKL）诱导的小鼠股骨松质骨丢失。这些在体外和体内的结果表明，动力蛋白的GTdR活性是破骨细胞的骨吸收活性的关键和dynasore是一个种子的开发新的抗再吸收剂。
The cytoskeletal organization of osteoclasts is required for bone resorption. Binding of dynamin with guanosine triphosphate (GTP) was previously suggested to be required for the organization of the actin cytoskeleton. However, the role of the GTPase activity of dynamin in the organization of the actin cytoskeleton as well as in the bone-resorbing activity of osteoclasts remains unclear. This study investigated the effects of dynasore, an inhibitor of the GTPase activity of dynamin, on the bone-resorbing activity of and actin ring formation in mouse osteoclasts in vitro and in vivo. Dynasore inhibited the formation of resorption pits in osteoclast cultures by suppressing actin ring formation and rapidly disrupting actin rings in osteoclasts. A time-lapse image analysis showed that dynasore shrank actin rings in osteoclasts within 30 min. The intraperitoneal administration of dynasore inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced trabecular bone loss in mouse femurs. These in vitro and in vivo results suggest that the GTPase activity of dynamin is critical for the bone-resorbing activity of osteoclasts and that dynasore is a seed for the development of novel anti-resorbing agents.