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

Takayuki Furumatsu, Emi Matsumoto, Tomoko Kanazawa, Masataka Fujii, Zhichao Lu, Ryotaro Kajiki, Toshihumi Ozaki

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Physiologic mechanical stress stimulates expression of chondrogenic genes, such as multifunctional growth factor CYR61/CTGF/NOV (CCN) 2 and α1(II) collagen (COL2A1), and maintains cartilage homeostasis. In our previous studies, cyclic tensile strain (CTS) induces nuclear translocation of transforming growth factor (TGF)-β receptor-regulated Smad2/3 and the master chondrogenic transcription factor Sry-type 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-β1 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-β1 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 CTS 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-β1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3.

Original languageEnglish
Pages (from-to)1508-1515
Number of pages8
JournalJournal of Biomechanics
Volume46
Issue number9
DOIs
Publication statusPublished - May 31 2013

Fingerprint

Tensile strain
Transforming Growth Factors
Gene Expression
Mechanical Stress
Growth Factor Receptors
Chromatin Immunoprecipitation
Luciferases
Gene expression
Cartilage
Intercellular Signaling Peptides and Proteins
Homeostasis
Transcription Factors
Collagen
Chemical activation
Transcription factors
Transcription
Assays
Genes

Keywords

  • CCN2
  • Cyclic tensile strain
  • SOX9
  • TGF-β receptor-regulated Smad2/3
  • Type II collagen

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rehabilitation
  • Biophysics
  • Biomedical Engineering

Cite this

Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-β-Smad2/3 pathway in chondrocytic cells. / Furumatsu, Takayuki; Matsumoto, Emi; Kanazawa, Tomoko; Fujii, Masataka; Lu, Zhichao; Kajiki, Ryotaro; Ozaki, Toshihumi.

In: Journal of Biomechanics, Vol. 46, No. 9, 31.05.2013, p. 1508-1515.

Research output: Contribution to journalArticle

Furumatsu, Takayuki ; Matsumoto, Emi ; Kanazawa, Tomoko ; Fujii, Masataka ; Lu, Zhichao ; Kajiki, Ryotaro ; Ozaki, Toshihumi. / Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-β-Smad2/3 pathway in chondrocytic cells. In: Journal of Biomechanics. 2013 ; Vol. 46, No. 9. pp. 1508-1515.
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AU - Ozaki, Toshihumi

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