Mechano-sensing in cells is tightly obliged with changes in intracellular free calcium (IFC), regulation of specific genes and activation of specific second messenger systems. To investigate whether single non-professional cells like osteoblasts can detect microgravity through the mechano-sensor, measurements on a sub-orbital rocket and parabolic flights observing the IFC and gene expression were performed. We find that microgravity did neither effect IFC nor gene expression. Thermal and mechanical noise within cells is too high in relation to the change of force due to the change from gravity to microgravity. Complementary force measurements have shown that cells exert high forces on the substrate and that these high forces have to be applied for activation.