Comparing the Roles of Bone Cells and Marrow Cells in the Adaptive Response of Bone to Loading

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A healthy skeleton is essential to maintaining an active lifestyle. Bones grow stronger when subjected to regular loading from exercise or daily activities. Conversely, they become more fragile during prolong inactivity or when the applied forces are below normal, such as during space flight or prolonged bed rest. Exploiting the underlying mechanisms of this phenomenon may provide new methods to combat bone loss due to aging and disease. The process of bone adaptation is controlled by the coordinated activity of cells embedded inside the bone and with cells in the bone marrow, but the potential for each family of cells to act independently is not known. In this project, small samples of bone will be kept alive in an incubator with mechanical loading applied to stimulate new bone growth. The response of cells within the bone and in the bone marrow will be detected and compared in order to identify potential ways to most effectively target them individually or in combination to maintain bone strength. The insights gained in this research have the potential to inform future investigations into novel pharmacological treatments to prevent bone loss. Furthermore, the research will have an educational impact through an established relationship with a local high school to encourage a broader participation in science and engineering and a continued international collaboration with the University of Ireland, Galway. Bone adaptation relies on the coordinated activity of osteoblasts, osteoclasts, and osteocytes. Osteocytes act as the primary sensors of bone deformation and signal neighboring cells to affect bone formation and resorption. However, many cells resident in the bone marrow are also mechanosensitive, and could contribute to the adaptive response of bone. This study will employ ex vivo mechanical stimulation applied to trabecular explants to study its effects in both bone marrow and osteocytes. Low magnitude mechanical stimulation (LMMS) will be used to induce shear stress in bone marrow while the small acceleration and mass of the bone result in effectively no bone deformation. Computational models will be used to quantify the marrow shear stress, which will be spatially correlated to bone formation. The effects of LMMS on beta-catenin signaling will be quantified in the presence of both agonists and antagonists to WNT signaling to identify the mechanobiological mechanisms that act within the marrow cells.