In orthodontics, various forms of mechanical stimulation induce opposing bone metabolism mechanisms. Bone resorption and bone formation occur in areas of compressive and tensile force action, respectively. The mechanism that causes such a difference in bone metabolism is still unclear. In this study, we investigated the difference in the osteoblastic calcium signaling response between compression and stretching mechanical stimuli. We applied two types of mechanical stimuli to osteoblast-like MC3T3-E1 cells: first microneedle direct indentation onto the cell as compression stimuli, and second stretching stimuli by using originally developed cell stretching MEMS device. Cells were treated with thapsigargin and calcium-free medium to investigate the source of the calcium ion. The results demonstrated variations in the osteoblastic calcium signaling response between the compression and stretching stimuli. The magnitude of an increase in the intracellular calcium ion concentration is much higher in the compression stimuli-applied cell group. Treatment of calcium-free medium nearly suppressed the calcium signaling response to both types of mechanical stimulation. Thapsigargin treatment induced an increase in the magnitude of calcium signaling response to the compression stimuli, while suppressed the slow and sustained increase in the calcium ion concentration in the stretching stimuli-applied cell group. These findings demonstrate the difference in the characteristics of osteoblastic calcium signaling response between compression and stretching mechanical stimuli.

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