Downregulation of decorin and transforming growth factor-beta1 by decorin gene suppression in tendinocytes.
Scars 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.
Hosaka
Yoshinao
Y
Department of Veterinary Anatomy, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan. hosap@rakuno.ac.jp
Kirisawa
Rikio
R
Mafune
Naoki
N
Takehana
Kazushige
K
D000818:Animals; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D058575:Decorin; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D013710:Tendons / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
D018076:DNA, Complementary; D058575:Decorin; D016326:Extracellular Matrix Proteins; D009838:Oligodeoxyribonucleotides; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1