Low-Rac1 activity downregulates MC3T3-E1 osteoblastic cell motility on a nanoscale topography prepared on polystyrene substrates in vitro.

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.