Mechanotransduction pathways in bone: calcium fluxes and the role of voltage-operated calcium channels

Changes in strain distribution across the vertebrate skeleton induce modelling and remodelling of bone structure. This relationship, like many in biomedical science, has been recognised since the 1800s, but it is only the recent development of in vivo and in vitro models that is allowing detailed investigation of the cellular mechanisms involved. A number of secondary messenger pathways have been implicated in load transduction by bone cells, and many of these pathways are similar to those proposed for other load-responsive cell types. It appears that load transduction involves interaction between several messenger pathways, rather than one specific switch. Interaction between these pathways may result in a cascade of responses that promote and maintain bone cell activity in remodelling of bone. The paper outlines research on the early rapid signals for load transduction and, in particular, activation of membrane channels in osteoblasts. The involvement of calcium channels in the immediate load response and the modulation of intracellular calcium as an early signal are discussed. These membrane channels present a possible target for manipulation in the engineering of bone tissue repair.