title: The influence of delayed compressive stress on TGF-β1-induced chondrogenic differentiation of rat BMSCs through Smad-dependent and Smad-independent pathways.
abstract: Mechanical stimuli play important roles in regulating chondrogenic differentiation, but seldom studies have focused on when and how mechanical stimuli should be initiated. We have previously shown that Col2α1 mRNA was increased by delayed dynamic compressive stress initiated at the 8th day of chondrogenic culture. The current work is to further study the possibility of using delayed mechanical stress to relay chondrogenesis initiated by exogenous TGF-β1. Mechanical stimulation was delivered from day 8 to day 14 of chondrogenic culture. It showed that delayed compressive stress not only stimulated gene expression and protein synthesis of chondrocyte-specific markers, but also stimulated the endogenous TGF-β1 gene transcription, protein expression and the subsequent activation even when exogenous TGF-β1 was discontinued. Furthermore, mechanical stress also promoted protein phosphorylation and nuclear translocation of Smad2/3, the TGF-β1 downstream effectors. Inhibition TGF-β with SB431542 significantly affected the stress-induced chondrogenic gene expression. In addition, phosphorylated-p38 and RhoB were upregulated by delayed loading in a TGF-β-related manner. Phosphorylated-ERK1/2 and Wnt7a were also increased, but in a TGF-β-independent way. It indicates that delayed compressive stress can be used as an effective substitute for TGF-β1 supplement in inducing chondrogenic differentiation.
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China. alibaba1998@sina.com.cn
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yuanwen
authors.initials: Y
authors.lastname: Zou
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Long
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Lijun
authors.initials: L
authors.lastname: Tan
authors.forename: Rui
authors.initials: R
authors.lastname: Ye
authors.forename: Xuejin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhihe
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects; D020219:Chondrogenesis / Q000187:drug effects*; D004149:Dioxoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D051896:Smad Proteins, Receptor-Regulated / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical; D054457:Tissue Scaffolds / Q000737:chemistry; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D051896:Smad Proteins, Receptor-Regulated; D053773:Transforming Growth Factor beta1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases