In this thesis, three factors that modulate mechanotransduction in bone cells were examined.

The first factor examined was the interaction of osteoblasts with various substrates. Modifications of implant surfaces, such as extracellular matrix (ECM) protein coating, have previously been performed to promote osseointegration. Osteoblasts adhered to various ECM protein coated surfaces had higher adhesion strength, focal adhesion kinase activation, F-actin fiber formation, and apparent elastic moduli compared to osteoblasts adhered to surfaces that promoted non-integrin mediated binding. Furthermore, osteoblasts adhered to ECM had significantly higher prostaglandin secretion compared to osteoblasts on glass only when subjected to fluid shear. These findings support the idea that substrates can modulate the mechanosensitivity of osteoblasts.

The second factor examined was the interaction between osteoblasts and osteocytes. Using a novel trabecular bone explant culture model, the effect of the presence of live osteocytes and dynamic hydrostatic pressure (DHP) loading on osteoblast anabolic activities was examined. The effect of the presence of osteoblasts and DHP on osteocyte viability was also examined. The presence of live osteocytes significantly increased osteoid formation, and increases in osteoid formation with DHP loading were only seen in explants with live osteocytes. Also, osteocyte viability was significantly enhanced by DHP loading. These findings support the idea that osteocytes play an important role in sensing mechanical stimuli and in modulating osteoblast response to the mechanical stimuli.

The third factor examined was the geometric parameters of bone cell networks. Micropatteming techniques were used to create bone cell networks with a controlled cell separation distance of 50 or 75pm and a connectivity of 4 neighbors. Single bone cells in this network were mechanically stimulated, and the propagation of calcium transients was examined. Although transmission speeds and magnitudes of calcium responses were not significantly different between networks of different separation distances, the percentage of responsive cells 2 cells away from the indented cell was significantly lower in networks with 75 pm separation. Some cells were able to respond twice through calcium signals traveling from two different cell paths. The ability of cells in the network to respond multiple times suggests a possible mechanism for mechano-memory in bone.