[Space flight/bedrest immobilization and bone. Signaling cascade induced by mechanical stress]

Mechanical stress to bone plays an important role in the maintenance of bone homeostasis. Mechanical stress initiates multiple signaling pathways in osteocytes and osteoblasts. Mechanical stress to bone induces fluid shear stress (FSS) caused by a change in extracellular fluid flow. FSS induces Ca(2+) influx that activates downstream CREB-AP-1-IL-11 signaling as well as nitric oxide synthesis. Interaction of integrins with matrix proteins such as periostin also activates intracellular signaling. These signaling pathways appear to enhance osteoblast differentiation and bone formation via Wnt/β-catenin signaling. The elucidation of signaling cascade in response to mechanical stress can lead to the development of new therapeutic agents.