Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity.
Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity.
复制标题
DOI：
10.2478/s11658-011-0006-z
复制
发表时间：
2011-06
影响因子：
8.3
通讯作者：
Kobayashi N
中科院分区：
文献类型：
--
作者：
Zhang X;Li C;Gao H;Nabeka H;Shimokawa T;Wakisaka H;Matsuda S;Kobayashi N
我们研究了Rho相关激酶（ROCK）对原代人成骨细胞和Saos-2人骨肉瘤细胞迁移和细胞骨架组织的影响。将两种细胞类型暴露于两种不同的ROCK抑制剂Y-27632和HA-1077。在本研究中使用的改进的运动性测定中，Y-27632和HA-1077以剂量依赖性和可逆的方式显著增加成骨细胞和骨肉瘤细胞在塑料上的迁移。荧光图像显示，用Y-27632或HA-1077培养的两种类型的细胞均表现出星状外观，应力纤维和焦点接触组装不良。蛋白质印迹显示ROCK抑制剂在5分钟内减少肌球蛋白轻链（MLC）磷酸化，而不影响整体肌球蛋白轻链蛋白水平。ROCK活性的抑制被认为可以通过肌动蛋白细胞骨架的重组和肌球蛋白活性的调节来增强人类成骨细胞的迁移。ROCK抑制剂可能作为合成代谢剂用于增强骨和关节假体的生物相容性。
We investigated the effects of Rho-associated kinase (ROCK) on migration and cytoskeletal organization in primary human osteoblasts and Saos-2 human osteosarcoma cells. Both cell types were exposed to two different ROCK inhibitors, Y-27632 and HA-1077. In the improved motility assay used in the present study, Y-27632 and HA-1077 significantly increased the migration of both osteoblasts and osteosarcoma cells on plastic in a dose-dependent and reversible manner. Fluorescent images showed that cells of both types cultured with Y-27632 or HA-1077 exhibited a stellate appearance, with poor assembly of stress fibers and focal contacts. Western blotting showed that ROCK inhibitors reduced myosin light chain (MLC) phosphorylation within 5 min without affecting overall myosin light-chain protein levels. Inhibition of ROCK activity is thought to enhance the migration of human osteoblasts through reorganization of the actin cytoskeleton and regulation of myosin activity. ROCK inhibitors may be potentially useful as anabolic agents to enhance the biocompatibility of bone and joint prostheses.