Laboratory for the Study of Molecular Biointerfaces, Department of Oral Histology and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.
J Biomed Mater Res A. 2013 Jun;101(6):1629-36. doi: 10.1002/jbm.a.34463. Epub 2012 Nov 27.
Surface roughness affects various cell activities, including osteoblast motility, which may have an effect on bone regeneration. Defective cell signaling, which is associated with the slow motility of osteoblasts on a substrate with rough topology at nanometer dimensions (Ra = 123.8 ± 29.1 nm), was studied. Osteoblasts grown on the rough surface at nanometer dimensions showed the high activities of small GTPase RhoA and Rho-associated kinase (ROCK) on the rough surface at nanometer dimensions and downregulated Rac1 activity compared to the smooth surface. The inhibition of ROCK in the cells with Y-27632, a specific ROCK inhibitor, reversed the low-cell motility. In addition, the transfection of constitutively active Rac1 reversed the low-cell motility. However, Rac1 inhibition abolished the reversal of low-cell motility induced by ROCK inhibition. These results indicate that upregulated RhoA/ROCK activity suppresses Rac1 activity to decrease the motility of osteoblasts on a rough surface at nanometer dimensions, and the low motility of osteoblasts on a rough surface at nanometer dimensions can be reversed by ROCK inhibition.
表面粗糙度会影响各种细胞活动，包括成骨细胞的迁移能力，而这可能会对骨再生产生影响。研究了与纳米级粗糙拓扑结构（Ra=123.8±29.1nm）表面上成骨细胞迁移缓慢相关的缺陷细胞信号转导。与光滑表面相比，在纳米级粗糙表面上生长的成骨细胞表现出小 GTPase RhoA 和 Rho 相关激酶（ROCK）的高活性，而 Rac1 的活性则被下调。用 Rho 激酶（ROCK）的特异性抑制剂 Y-27632 抑制 ROCK 会逆转低细胞迁移。此外，转染组成性激活的 Rac1 可逆转低细胞迁移。然而，Rac1 抑制消除了 ROCK 抑制诱导的低细胞迁移的逆转。这些结果表明，上调的 RhoA/ROCK 活性抑制 Rac1 活性，从而降低纳米级粗糙表面上成骨细胞的迁移能力，并且可以通过抑制 ROCK 来逆转纳米级粗糙表面上成骨细胞的低迁移能力。
