Bone cells interact in vivo with extracellular matrices mainly formed of type-I collagen, for which the mineral content changes during the bone remodeling cycle. Bone mineral, which is apatitic in nature, was shown to respectively increase and alter the activity and form of osteoblasts. In order to study the micro-environmental effects of the matrix on the preliminary steps of bone formation, it was hypothesized that these morphological alterations could explain the increased activity of the osteoblastic cells by enhancing their mecano-sensibility. This altered mechano-sensibility could in turn modify the osteoblastic cells' response to the widely perceived micro-vibrations in vivo. It was demonstrated that, on the collagen-mineralized materials ACC (Apatite Collagen Complex), MC3T3-E1 pre-osteoblastic cells formed a matrix rich in osteopontin, fibronectin and angiogenic factors. At the same time, an increase in cell adhesion and migration dependent on the mineral content was seen. We also observed an enhanced mechano-sensibility (increased focal adhesion gene expression and turn-over) when cells were cultured on ACC. Furthermore, it was found that the vibratory stimuli response was up-regulated on non-mineralized materials (information) and downregulated on ACC (stress) vs. non-stimulated substrates. This observation was interpreted as a hypersensitization to environmental cues on ACC. Taken together, these data have demonstrated that pre-osteoblastic cell mechanic alterations on ACC give rise to a specific functionalization mimicking what is observed in vivo in the cement line required for bone-formation. ACC-related mechano-sensibility changes, which render ACC a mechanomimetic substrate and lead us to compare the observed cell behavior with osteocytes, could explain the specific matrix deposition and altered response to vibrations. The final goal of establishing a model for in vitro bone remodeling can only be fulfill by considering physico-chemical parameters of the bonematrix and cocultures
