[Osteoporosis and Mechano-biosciences.]

Mechanical unloading due to long-term bedrest or microgravity during spaceflight causes a devastating influence on bone. Although bisphosphonates can prevent bone loss and hypercalciuria by mechanical unloading for up to 6 months, the influence of unloading for longer period of time is unknown. This is because mechanical loading is one of the most important stimuli for bone formation. Mechanical stress activates several intracellular signaling pathways. Among them, activation of stress-activated cation channel by fluid shear stress stimulates ERK-CREB signaling to enhance the expression of fos family transcription factors, which stimulates IL-11 expression in osteoblastic cells. IL-11 then enhances Wnt/β-catenin signaling, by suppressing the expression of Wnt/β-catenin inhibitors, sclerostin and Dkks. Because Wnt/β-catenin signal enhances responsiveness to mechanical stimuli, stimulation of Wnt/β-catenin signaling may increase the effect of exercise in maintaining axial bone mass.