title: YAP and ERK mediated mechanical strain-induced cell cycle progression through RhoA and cytoskeletal dynamics in rat growth plate chondrocytes.
abstract: Yes-associated protein (YAP) and extracellular signal-regulated kinase (ERK) have been considered as key regulators in tissue homeostasis, organ development, and tumor formation. However, the roles of YAP and ERK in the mediating strain mechanosensing in the growth plate cartilage have not been determined. In this study, chondrocytes obtained from the growth plate cartilage of 2-week-old Sprague-Dawley rats were subjected to the mechanical strain with different magnitudes and durations at a frequency of 0.5 Hz. We found that YAP and ERK activation in response to mechanical strain was time and magnitude dependent. Pretreatment with a RhoA inhibitor (C3 toxin) or a microfilament cytoskeleton disrupting reagent (cytochalasin D) could suppress their activation. In addition, activated YAP and ERK were able to induce cell cycle progression by up-regulating the expression of cell cycle-related genes. These results shed new light on the function of YAP and ERK in mechanical strain-promoted growth plate development. Our results also provided evidence that RhoA and cytoskeletal dynamics are required for this mechanotransduction. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1121-1129, 2016.
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.|Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, Jiangsu Province, P. R. China.
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Yingxing
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, Jiangsu Province, P. R. China.
authors.forename: Chengyuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, Jiangsu Province, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Pi
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Anmin
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Fengjing
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002453:Cell Cycle; D019902:Chondrocytes / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006132:Growth Plate / Q000166:cytology / Q000201:enzymology; D020935:MAP Kinase Signaling System; D040542:Mechanotransduction, Cellular; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D000091102:YAP-Signaling Proteins; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000091102:YAP-Signaling Proteins; C509425:Yap1 protein, rat; D048049:Extracellular Signal-Regulated MAP Kinases; C000621224:RhoA protein, rat; D020741:rho GTP-Binding Proteins
keywords: extracellular signal-regulated kinase (ERK); growth plate chondrocytes; mechanical strain; mechanotransduction; yes-associated protein (YAP)