Osteocytes are believed to be the mechanosensory cells that detect and respond to mechanical loading. Physiological loading by oscillatory fluid flow (OFF) activates osteocytes to increase intracellular calcium concentration and release prostaglandin E2 (PGE2). Osteocytes are also sensitive to chemical stimulations such as serotonin, which can also increase PGE2 release. However, it is unclear whether mechanical stimulation can influence osteocyte sensitivity towards serotonin. In this thesis, MLO-Y4 osteocyte-like cells were subjected to serotonin with or without precondition by OFF, the responses of intracellular calcium and PGE2 release were measured. Serotonin increased intracellular calcium and PGE2 release in osteocytes. The effects were significantly reduced by OFF precondition, suggesting mechanical precondition by OFF can reduce osteocyte sensitivity towards serotonin. In terms of mechanisms, OFF- and serotonin-induced calcium responses depended on intra- and extracellular calcium stores. ATP was found to partially mediate OFF modulation of serotonin-induced PGE2 release but not calcium.

Osteocytes are believed to be the mechanosensory cells that detect and respond to mechanical loading. Physiological loading by oscillatory fluid flow (OFF) activates osteocytes to increase intracellular calcium concentration and release prostaglandin E2 (PGE2). Osteocytes are also sensitive to chemical stimulations such as serotonin, which can also increase PGE2 release. However, it is unclear whether mechanical stimulation can influence osteocyte sensitivity towards serotonin. In this thesis, MLO-Y4 osteocyte-like cells were subjected to serotonin with or without precondition by OFF, the responses of intracellular calcium and PGE2 release were measured. Serotonin increased intracellular calcium and PGE2 release in osteocytes. The effects were significantly reduced by OFF precondition, suggesting mechanical precondition by OFF can reduce osteocyte sensitivity towards serotonin. In terms of mechanisms, OFF- and serotonin-induced calcium responses depended on intra- and extracellular calcium stores. ATP was found to partially mediate OFF modulation of serotonin-induced PGE2 release but not calcium.