title: Periodic mechanical stress activates EGFR-dependent Rac1 mitogenic signals in rat nucleus pulpous cells via ERK1/2.
abstract: The mitogenic effects of periodic mechanical stress on nucleus pulpous cells have been studied extensively but the mechanisms whereby nucleus pulpous cells sense and respond to mechanical stimulation remain a matter of debate. We explored this question by performing cell culture experiments in our self-developed periodic stress field and perfusion culture system. Under periodic mechanical stress, rat nucleus pulpous cell proliferation was significantly increased (p < 0.05 for each) and was associated with increases in the phosphorylation and activation of EGFR, Rac1, and ERK1/2 (p < 0.05 for each). Pretreatment with the ERK1/2 selective inhibitor PD98059 reduced periodic mechanical stress-induced nucleus pulpous cell proliferation (p < 0.05 for each), while the activation levels of EGFR and Rac1 were not inhibited. Proliferation and phosphorylation of ERK1/2 were inhibited after pretreatment with the Rac1 inhibitor NSC23766 in nucleus pulpous cells in response to periodic mechanical stress (p < 0.05 for each), while the phosphorylation site of EGFR was not affected. Inhibition of EGFR activity with AG1478 abrogated nucleus pulpous cell proliferation (p < 0.05 for each) and attenuated Rac1 and ERK1/2 activation in nucleus pulpous cells subjected to periodic mechanical stress (p < 0.05 for each). These findings suggest that periodic mechanical stress promotes nucleus pulpous cell proliferation in part through the EGFR-Rac1-ERK1/2 signaling pathway, which links these three important signaling molecules into a mitogenic cascade.
authors.affiliation: Department of Orthopedics, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou 213003, China.
authors.forename: Gongming
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Clinical Pharmacy, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou 213003, China.
authors.forename: Nanwei
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou 213003, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The Affiliated Changzhou No. 2 Hospital of Nanjing Medical University, Changzhou 213003, China. Electronic address: lumingnong@hotmail.com.
authors.forename: Luming
authors.initials: L
authors.lastname: Nong
authors.affiliation: Department of Orthopedics, The Affiliated Jiangyin Hospital of Southeast University Medical School, Jiangyin 214400, China. Electronic address: keweiren@hotmail.com.
authors.forename: Kewei
authors.initials: K
authors.lastname: Ren
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007403:Intervertebral Disc / Q000166:cytology* / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008938:Mitosis / Q000502:physiology; D050258:Mitosis Modulators / Q000378:metabolism; D010766:Phosphorylation; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013312:Stress, Physiological / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D050258:Mitosis Modulators; C483803:Egfr protein, rat; D066246:ErbB Receptors; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: EGFR; ERK1/2; Nucleus pulpous cell proliferation; Periodic mechanical stress; Rac1