title: Prostaglandin E2 modulates F-actin stress fiber in FSS-stimulated MC3T3-E1 cells in a PKA-dependent manner.
abstract: The effect of prostaglandin E2 (PGE2) on bone mass has been well-established in vivo. Previous studies have showed that PGE2 increases differentiation, proliferation, and regulates cell morphology through F-actin stress fiber in statically cultured osteoblasts. However, the effect of PGE2 on osteoblasts in the presence of fluid shear stress (FSS), which could better uncover the anabolic effect of PGE2 in vivo, has yet to be examined. Here, we hypothesized that PGE2 modulates F-actin stress fiber in FSS-stimulated MC3T3-E1 osteoblastic cells through protein kinase A (PKA) pathway. Furthermore, this PGE2-induced F-actin remodeling was associated with the recovery of cellular mechanosensitivity. Our data showed that treatment with 10 nM dmPGE2 for 15 min significantly suppressed the F-actin stress fiber intensity in FSS-stimulated cells in a PKA-dependent manner. In addition, dmPGE2 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 dmPGE2 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 PGE2 increased bone formation as shown in vivo, suggesting that PGE2 could be a potential target for treatments of bone formation-related diseases.
authors.affiliation: Key Laboratory for Biorheological Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Gong
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.forename: Liyun
authors.initials: L
authors.lastname: Wang
authors.forename: Randall L
authors.initials: RL
authors.lastname: Duncan
authors.forename: Jun
authors.initials: J
authors.lastname: Pan
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology*; D000199:Actins / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology*; D008954:Models, Biological; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D022502:Stress Fibers / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D000199:Actins; D017868:Cyclic AMP-Dependent Protein Kinases; D015064:16,16-Dimethylprostaglandin E2
keywords: PKA pathway; cytoskeleton; fluid shear stress (FSS); intracellular calcium; prostaglandin E2