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ID 51099
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Author
Matsumoto, Emi
Kanazawa, Tomoko
Fujii, Masataka
Lu, Zhichao
Kajiki, Ryotaro
Abstract
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.
Keywords
Cyclic tensile strain
TGF-beta receptor-regulated Smad2/3
CCN2
SOX9
Type II collagen
Published Date
2013-05-31
Publication Title
Journal of Biomechanics
Volume
volume46
Issue
issue9
Publisher
Elsevier Sci Ltd.
Start Page
1508
End Page
1515
ISSN
0021-9290
NCID
AA00694200
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1016/j.jbiomech.2013.03.028
language
英語
Copyright Holders
(C) 2013 Elsevier Ltd. All rights reserved.
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Refereed
True
DOI
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