The osteocyte as a wiring transmission system

The mechanism of transduction of mechanical strains into biological signals remains one of the more baffling problems of skeletal homeostasis. The updated literature ascribes to osteocytes the function of sensing the strains induced into the bone matrix by mechanical stresses. Whether the osteocytes perform such function by themselves or they are helped by other cells is also unknown. Indeed TEM investigations carried out in our laboratory pointed out the existence of a functional syncytium among all the cells of the osteogenic lineage (COL; stromal cells, osteoblasts or bone lining cells, osteocytes). On the basis of this finding, we suggested that COL may reciprocally modulate their function not only by volume transmission (paracrine and autocrine stimulation) but also by wiring transmission, namely in a neuronal like manner. Thanks to their location, osteocytes should theoretically be the first cells of COL functional syncytium to sense mechanical strains, whereas stromal cells should be the first to be activated by hormonal molecules diffusing across the endothelial lining. Since PTH and Estrogen receptors have also been localized on osteocytes, and considering that such hormones have been suggested to modulate the sensitivity to strain of the bone mechanosensor, we suggested that the osteocyte syncytium may constitute the microscopic bone structure that sense both mechanical strain and biochemical factors and, at any moment, after having combined the two types of stimuli, issues the appropriate signals to the other bone cells by volume and/or wiring-transmission. Stromal cells, on the other hand, besides transmitting signals from vascular endothelium to bone cells, may control the differentiation and then direct the course of the osteoblasts around the vascular framework.