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Investigating solute transport in bone: implications on cell-to-cell signaling and drug delivery Recent experiments strongly suggest that osteocytes, the most numerous bone cells, play a more active role in bone adaptation and metabolism than previously thought. These multi-functioning cells form a sensor network that can detect external mechanical stimuli. In response, they release soluble agents (e.g., OPG, RANKL, NO, PGE2, and sclerostin) that can modulate the function of other cell types, such as osteoclastic-targeted resorption during overuse and disuse and load-induced osteoblastic bone formation. Solute transport through the mineralized bone matrix is essential for osteocyte survival and normal function (cell-to-cell signaling). However, solute flows in bone are poorly understood and inadequately quantified, due to technical difficulties of working with mineralized matrix. In this talk, I will share with you our new approach to attack this difficult problem, combining minimally invasive imaging and mathematical modeling. The implications of these in situ and in vivo measurements will be discussed.