Transcriptional pathways induced by fluid shear stress in mouse preosteoblast cells.

Recent findings support the idea that fluid movement in the bone is a key factor in bone formation and related cellular responses. However, the precise molecular mechanisms are not known. Our data demonstrates that fluid shear stress is a key factor in the activation of specific transcriptional pathways in murine preosteoblast (MC3T3E1) cells. MC3T3E1 cells have increased expression of the egr-1 and p57kip2 genes after being subjected to 0.3 dynes/cm2 of fluid shear stress. The MC3T3E1 cells are already known to express egr-1, a multipotent transcription factor, after high levels of fluid shear stress, but this is the first demonstration of egr-1 expression after low levels of fluid shear stress. Moreover, this is the first study showing expression of p57kip2 by the MC3T3E1 cells after fluid shear stress. The expression of p57kip2, a cyclin dependent kinase inhibitor, is a strong indicator that the cells are exiting the cell cycle and are beginning to differentiate. Our data shows decreased 3H-thymidine incorporation up to 18 hours post stress, which agrees with the upregulation of p57kip2 as a result of fluid shear stress.