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ID 51099
フルテキストURL
著者
Furumatsu, Takayuki Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr
Matsumoto, Emi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr
Kanazawa, Tomoko Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr
Fujii, Masataka Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr
Lu, Zhichao Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr
Kajiki, Ryotaro Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr
Ozaki, Toshifumi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Orthopaed Surg Sci Funct Recovery & Reconstr
抄録
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.
キーワード
Cyclic tensile strain
TGF-beta receptor-regulated Smad2/3
CCN2
SOX9
Type II collagen
発行日
2013-05-31
出版物タイトル
Journal of Biomechanics
46巻
9号
出版者
Elsevier Sci Ltd.
開始ページ
1508
終了ページ
1515
ISSN
0021-9290
NCID
AA00694200
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1016/j.jbiomech.2013.03.028
言語
English
OAI-PMH Set
岡山大学
著作権者
(C) 2013 Elsevier Ltd. All rights reserved.
論文のバージョン
author
査読
有り
DOI
Web of Sience KeyUT