title: A novel role for integrin-linked kinase in periodic mechanical stress-mediated ERK1/2 mitogenic signaling in rat chondrocytes.
abstract: In recent years, a variety of studies have been performed to investigate the cellular responses of periodic mechanical stress on chondrocytes. Integrin β1-mediated ERK1/2 activation was proven to be indispensable in periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. However, other signal proteins responsible for the mitogenesis of chondrocytes under periodic mechanical stress remain incompletely understood. In the current investigation, we probed the roles of integrin-linked kinase (ILK) signaling in periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. We found that upon periodic mechanical stress induction, ILK activity increased significantly. Depletion of ILK with targeted shRNA strongly inhibited periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis. In addition, pretreatment with a blocking antibody against integrin β1 resulted in a remarkable decrease in ILK activity in cells exposed to periodic mechanical stress. Furthermore, inhibition of ILK with its target shRNA significantly suppressed ERK1/2 activation in relation to periodic mechanical stress. Based on the above results, we identified ILK as a crucial regulator involved in the integrin β1-ERK1/2 signal cascade responsible for periodic mechanical stress-induced chondrocyte proliferation and matrix synthesis.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Huanghe
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Zhefeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Weiding
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Jinchun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, 300 Guang Zhou Road, Nanjing, 210029, China.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology* / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D013314:Stress, Mechanical; D000099200:Scaffold Protein ILK
chemical_list: D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: ILK; chondrocyte proliferation; integrin β1; matrix synthesis; periodic mechanical stress