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Downregulation of decorin and transforming growth factor-beta1 by decorin gene suppression in tendinocytes.

AbstractScars formed after tendonitis result in altered tissue mechanical properties after injury. The interaction of collagen molecules with decorin affects collagen fibrogenesis, and scar tissue is fragile as a consequence of a large amount of decorin in the scar. We hypothesized that scar formation could be prevented by controlling decorin expression in tendinocytes. As a preliminary experiment, we treated tendinocytes with decorin antisense oligodeoxynucleotides (ODNs). Tendinocytes were isolated from Achilles tendons of New Zealand white rabbits and treated with ODN. When tendinocytes were transfected with decorin sense ODN, there was no alteration, whereas decorin antisense ODN-treated tendinocytes showed suppression of transforming growth factor (TGF)-beta1 production. Decorin and TGF-beta1-production of tendinocytes is regulated by decorin gene suppression. The results showed that the antisense approach is an attractive therapeutic strategy not only for preventing decorin deposition in scar tissue, which decreases collagen fibril diameter, but also for controlling TGF-beta1 production, which leads to organ fibrosis.
AuthorsYoshinao Hosaka, Rikio Kirisawa, Naoki Mafune, Kazushige Takehana (Affiliation: Department of Veterinary Anatomy, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan. hosap at rakuno.ac.jp)
JournalConnective tissue research (Connect Tissue Res) Vol. 46 Issue 1 Pg. 18-26 ( 2005) ISSN: 0300-8207 United States
PMID16019410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • DNA, Complementary
  • Extracellular Matrix Proteins
  • Oligodeoxyribonucleotides
  • Proteoglycans
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • decorin
Topics
  • Animals
  • Cells, Cultured
  • DNA, Complementary (genetics)
  • Down-Regulation
  • Extracellular Matrix Proteins (genetics, metabolism)
  • Immunohistochemistry
  • Male
  • Oligodeoxyribonucleotides (genetics)
  • Proteoglycans (genetics, metabolism)
  • RNA, Messenger (genetics)
  • Rabbits
  • Tendons (metabolism)
  • Transfection
  • Transforming Growth Factor beta (biosynthesis)
  • Transforming Growth Factor beta1