Gap junctions and fluid flow response in MC3T3-E1 cells

In the current study, we examined the role of gap junctions in oscillatory fluid flow-induced changes in intracellular Ca²⁺concentration and prostaglandin release in osteoblastic cells. This work was completed in MC3T3-E1 cells with intact gap junctional communication as well as in MC3T3-E1 cells rendered communication deficient through expression of a dominant-negative connexin. Our results demonstrate that MC3T3-E1 cells with intact gap junctions respond to oscillatory fluid flow with significant increases in prostaglandin E₂ (PGE₂) release, whereas cells with diminished gap junctional communication do not. Furthermore, we found that cytosolic Ca²⁺ (Ca${}_{\text{i}}^{2+}$ ) response was unaltered by the disruption in gap junctional communication and was not significantly different among the cell lines. Thus our results suggest that gap junctions contribute to the PGE₂ but not to the Ca${}_{\text{i}}^{2+}$ response to oscillatory fluid flow. These findings implicate gap junctional intercellular communication (GJIC) in bone cell ensemble responsiveness to oscillatory fluid flow and suggest that gap junctions and GJIC play a pivotal role in mechanotransduction mechanisms in bone.