title: 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.
authors.affiliation: Institute of Orthopaedics, The Lanzhou University Second Hospital, Lanzhou, Gansu Province, Peoples Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Yan-chao
authors.initials: YC
authors.lastname: Ma
authors.forename: Hai-li
authors.initials: HL
authors.lastname: Shen
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Hui-juan
authors.initials: HJ
authors.lastname: Cheng
authors.forename: Cui-fang
authors.initials: CF
authors.lastname: Wang
authors.forename: Ya-yi
authors.initials: YY
authors.lastname: Xia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D015536:Down-Regulation; D040542:Mechanotransduction, Cellular; D051379:Mice; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D048054:Mitogen-Activated Protein Kinase 7