| Human, animal and cell studies indicate that the application of vibrations can be anabolic and/or anti-catabolic to bone. Dynamic oscillations create a complex mechanical environment which generates forces not only through accelerations but also through fluid forces. The specific mechanical signal which cells respond has not been identified, in-part because the generated fluid shear is coupled with the magnitude of the applied acceleration in most in vivo and in vitro studies. Looking at how these two mechanical parameters previously proposed to drive the cellular response to vibration -- fluid shear and accelerations, act together is critical for understanding their effects on bone cell metabolism.;Overall aim of this dissertation was 1) Quantify the vibration-induced fluid shear stresses in vitro and test whether the separation of two mechanical parameters is possible to identify mechanical information carried by vibrations into both macro and cellular level. 2) Determine the possible interactions between vibration-induced mechanical information (acceleration, fluid shear, frequency) that would modulate cellular response to vibrations.;Our data demonstrated that peak shear stress can be effectively separated from peak acceleration by controlling specific levels of vibration frequency, acceleration, and/or fluid viscosity. Role of vibration specific mechanical components were further investigated using osteoblasts, osteocytes and mesenchymal stem cells. Fluid shear did not have a profound effect on vibration response of cells. Consistently across all the experiments, groups with lower fluid shear stress elicited higher or equal responses when compared to groups with higher fluid shear. Cellular mechanosensitivity to vibrations were specific to level of cell maturation/cytoskeletal remodeling and frequency. Level of cytoskeletal development was dependent on accelerations but not to fluid shear. When compared to accelerations, fluid shear induced smaller cellular deformations.;In conclusion, results presented in this dissertation indicated that cells can exclusively sense and respond to accelerations in the presence of fluid shear stresses. Results suggest that response of cells to vibrations induced signals converge on the forces created on the cytoskeleton, rather than independently affecting the cellular response. There exists a relationship exists between frequency, signal strength and cytoskeletal adaptation, offering that non-pharmacological potential of vibration treatment for bone loss can be directed towards cell specific populations. |
