Biomechanical force is one of the major epigenetic factors that determine the form and differentiation of skeletal tissues. In this study, osteoblastic cells UMR-106 were exposed to compressive forces at 1000 mustrain and 4000 mustrain via a four-point bending system, and analyzed by MTT and LSCM techniques. Cell proliferation activity decreased shortly after loading but recovered to normal levels within 24 h. And the cytoskeleton depolymerized at first, but then gradually repolymerized. To find out the role of cytoskeleton in mechanotransduction, we examined the relationship between cytoskeleton construction and c-fos expression. A transient stress-induced upregulation in c-fos mRNA and c-Fos protein was discovered when cells were exposed to physiological forces. And the upregulation in c-fos expression was blocked by cytochalasin D (Depolymerizing agent of microfilament). It gave clues that the organization of cytoskeleton was an important link in transcriptional control in response to low-mechanical stimulation.