Induction of NO and prostaglandin E2 in osteoblasts by wall-shear stress but not mechanical strain

The nature of the stimulus sensed by bone cells during mechanical usage has not yet been determined. Because nitric oxide (NO) and prostaglandin (PG) production appear to be essential early responses to mechanical stimulation in vivo, we used their production to compare the responsiveness of bone cells to strain and fluid flow in vitro. Cells were incubated on polystyrene film and subjected to unidirectional linear strains in the range 500-5,000 microstrain (microepsilon). We found no increase in NO or PGE2 production after loading of rat calvarial or long bone cells, MC3T3-E1, UMR-106-01, or ROS 17/2.8 cells. In contrast, exposure of osteoblastic cells to increased fluid flow induced both PGE2 and NO production. Production was rapidly induced by wall-shear stresses of 148 dyn/cm2 and was observed in all the osteoblastic populations used but not in rat skin fibroblasts. Fluid flow appeared to act through an increase in wall-shear stress. These data suggest that mechanical loading of bone is sensed by osteoblastic cells through fluid flow-mediated wall-shear stress rather than by mechanical strain.