Rho 激酶抑制剂通过调节肌动球蛋白活性刺激人培养成骨细胞的迁移。
Rho kinase inhibitors stimulate the migration of human cultured osteoblastic cells by regulating actomyosin activity.
机构信息
Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Ehime, Japan.
出版信息
Cell Mol Biol Lett. 2011 Jun;16(2):279-95. doi: 10.2478/s11658-011-0006-z. Epub 2011 Mar 9.
Abstract
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.
摘要
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。两种细胞类型均暴露于两种不同的 ROCK 抑制剂，Y-27632 和 HA-1077。在本研究中使用的改良迁移测定中，Y-27632 和 HA-1077 以剂量依赖和可逆的方式显著增加了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呈星状外观，应力纤维和焦点接触组装不良。Western blot 显示 ROCK 抑制剂在 5 分钟内降低肌球蛋白轻链（MLC）磷酸化，而不影响肌球蛋白轻链蛋白的总体水平。ROCK 活性的抑制被认为通过肌动蛋白细胞骨架的重排和肌球蛋白活性的调节来增强人成骨细胞的迁移。ROCK 抑制剂可能作为一种有潜力的促合成药物，增强骨和关节假体的生物相容性。
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