Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-β-Smad2/3 pathway in chondrocytic cells

被引：54

作者：

Furumatsu, Takayuki ^{[1
]}

Matsumoto, Emi ^{[1
]}

Kanazawa, Tomoko ^{[1
]}

Fujii, Masataka ^{[1
]}

Lu, Zhichao ^{[1
]}

Kajiki, Ryotaro ^{[1
]}

Ozaki, Toshifumi ^{[1
]}

机构：

[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr, Kita Ku, Okayama 7008558, Japan

来源：

JOURNAL OF BIOMECHANICS | 2013年 / 46卷 / 09期

基金：

日本学术振兴会;

关键词：

Cyclic tensile strain; TGF-beta receptor-regulated Smad2/3; CCN2; SOX9; Type II collagen; BOVINE ARTICULAR-CARTILAGE; MECHANICAL STRETCH; GENE-EXPRESSION; GROWTH; SOX9; COLLAGEN; PROTEIN; CHONDROGENESIS; TRANSCRIPTION; CHROMATIN;

D O I：

10.1016/j.jbiomech.2013.03.028

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

Physiologic mechanical stress stimulates expression of chondrogenic genes, such as multifunctional growth factor CYR61/CTGF/NOV (CCN) 2 and alpha 1(II) collagen (COL2A1), and maintains cartilage home-ostasis. In our previous studies, cyclic tensile strain (CTS) induces nuclear translocation of transforming growth factor (TGF)-beta receptor-regulated Smad2/3 and the master chondrogenic transcription factor Srytype HMG box (SOX) 9. However, the precise mechanism of stretch-mediated Smad activation remains unclear in transcriptional regulation of CCN2 and COL2A1. Here we hypothesized that CTS may induce TGF-beta 1 release and stimulate Smad-dependent chondrogenic gene expression in human chondrocytic SW1353 cells. Uni-axial CTS (0.5 Hz, 5% strain) stimulated gene expression of CCN2 and COL2A1 in SW1353 cells, and induced TGF-beta 1 secretion. CCN2 synthesis and nuclear translocalization of Smad2/3 and SOX9 were stimulated by CTS. In addition, CTS increased the complex formation between phosphorylated Smad2/3 and SOX9. The CCN2 promoter activity was cooperatively enhanced by CIS and Smad3 in luciferase reporter assay. Chromatin immunoprecipitation revealed that CTS increased Smad2/3 interaction with the CCN2 promoter and the COL2A1 enhancer. Our results suggest that CTS epigenetically stimulates CCN2 transcription via TGF-beta 1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1508 / 1515

页数：8

共 45 条

[1] Interleukin-1 in combination with oncostatin M up-regulates multiple genes in chondrocytes - Implications for cartilage destruction and repair [J].