Prostaglandin E2 modulates F-actin stress fiber in FSS-stimulated MC3T3-E1 cells in a PKA-dependent manner

The effect of prostaglandin E-2 (PGE(2)) on bone mass has been well-established in vivo. Previous studies have showed that PGE(2) increases differentiation, proliferation, and regulates cell morphology through F-actin stress fiber in statically cultured osteoblasts. However, the effect of PGE(2) on osteoblasts in the presence of fluid shear stress (FSS), which could better uncover the anabolic effect of PGE(2) in vivo, has yet to be examined. Here, we hypothesized that PGE(2) modulates F-actin stress fiber in FSS-stimulated MC3T3-E1 osteoblastic cells through protein kinase A (PKA) pathway. Furthermore, this PGE(2)-induced F-actin remodeling was associated with the recovery of cellular mechanosensitivity. Our data showed that treatment with 10 nM dmPGE(2) for 15 min significantly suppressed the F-actin stress fiber intensity in FSS-stimulated cells in a PKA-dependent manner. In addition, dmPGE(2) treatment enhanced the cells' calcium peak magnitude and the percentage of responding cells in the second FSS stimulation, though these effects were abolished and attenuated by co-treatment with phalloidin. Our results demonstrated that 10 nM dmPGE(2) was able to accelerate the 'reset' process of F-actin stress fiber to its pre-stimulated level partially through PKA pathway, and thus promoted the recovery of cellular mechanosensitivity. Our finding provided a novel cellular mechanism by which PGE(2) increased bone formation as shown in vivo, suggesting that PGE(2) could be a potential target for treatments of bone formation-related diseases.