The mechanism of transduction of mechanical strains into biological signals at the bone cellular level

As appears from the literature, the majority of bone researchers consider osteoblasts and osteoclasts the only very important bony cells. In the present report we provide evidence, based on personal morphofunctional investigations, that such a view is incorrect and misleading. Indeed osteoblasts and osteoclasts undoubtedly are the only bone forming and bone reabsorbing cells, but they are transient cells, thus they cannot be the first to be involved in sensing both mechanical and non-mechanical agents which control bone modeling and remodeling processes. Briefly, according to our view, osteoblasts and osteoclasts represent the arms of a worker; the actual operation center is constituted by the cells of the osteogenic lineage in the resting state. Such a resting phase is characterized by osteocytes, bone lining cells and stromal cells, all connected in a functional syncytium by gap junctions, which extends from the bone to the vessels. We named this syncytium the Bone Basic Cellular System (BBCS), because it represents the only permanent cellular background capable first of sensing mechanical strains and biochemical factors and then of triggering and driving both processes of bone formation and bone resorption. As shown by our studies, signalling throughout BBCS can occur by volume transmission (VT) and/or wiring transmission (WT). VT corresponds to the routes followed by soluble substances (hormones, cytokines etc.), whereas WT represents the diffusion of ionic currents along cytoplasmic processes in a neuron-like manner. It is likely that non-mechanical agents first affect stromal cells and diffuse by VT to reach the other cells of BBCS, whereas mechanical agents are first sensed by osteocytes and then issued throughout