Cytoskeletal reorganization mediates fluid shear stress‐induced ERK5 activation in osteoblastic cells

Abstract Mechanotransduction is a complicated process, of which mechanosensation is the first step. Previous studies have shown that the cytoskeleton plays a crucial role in mechanosensation and the mediation of intracellular signal transduction. However, the mechanism of mechanotransduction in the bone remains elusive. Here, we investigated the potential involvement of a novel MAPK (mitogen‐activated protein kinase) member, ERK5 (extracellular‐signal‐regulated kinase 5), in the response of osteoblastic cells to FSS (fluid shear stress). Our results demonstrated that ERK5 was rapidly phosphorylated in pre‐osteoblastic MC3T3‐E1 cells upon FSS, and the integrity and reorganization of the cytoskeleton were critical in this process, in which the cytoskeleton‐dependent activation of FAK (focal adhesion kinase) may be involved in the activation of ERK5 induced by FSS. Moreover, we found that cytoskeletal disruption led to significant down‐regulation of ERK5 phosphorylation, but had no effect on ERK5 nuclear localization. Furthermore, the cytoskeleton rapidly reorganized in response to FSS, but long‐time fluid load, even at a physiological level, led to cytoskeletal disruption, suggesting that other pathways may be involved in long‐term mechanotransduction. Taken together, our data provide new insight into the mechanisms of mechanosensation by highlighting the link between ERK5 activation and cytoskeletal reorganization in osteoblasts undergoing FSS.