Down-regulation of collagen synthesis and matrix metalloproteinase expression in myofibroblasts from dupuytren nodule using adenovirus-mediated relaxin gene therapy

Young Mi Kang, Yun Rak Choi, Chae Ok Yun, Jin Oh Park, Kyung Soo Suk, Hak Sun Kim, Moon Soo Park, Byung Ho Lee, Hwan Mo Lee, Seong Hwan Moon

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Dupuytren's disease is a fibroproliferative connective tissue disorder characterized by contracture of the palmer fascia of the hand. Relaxin (RLN) is a multifunctional factor which contributes to the remodeling of the pelvic ligament by inhibiting fibrosis and inflammatory activities. The aim of this study was to investigate the effect of the RLN gene on the inhibition of fibrosis in myofibroblastic cells. Myofibroblast cells with adenovirus LacZ (Ad-LacZ) as a marker gene or adenovirus relaxin (Ad-RLN) as therapeutic gene showed transgene expressions in beta-galactosidase assay and Western blot analysis. Myofibroblastic cells with Ad-RLN demonstrated a 22% and 48% reduction in collagen I and III mRNA expressions respectively, a 50% decrease in MMP-1, 70% decrease in MMP-2, 80% decrease in MMP-9, and a 15% reduction in MMP-13 protein expression compared with cultures with viral control and saline control. In addition, myofibroblastic cells with Ad-RLN showed a 40% decrease in TIMP 1 and a 15% increase in TIMP 3 protein expression at 48 h compared to cultures with viral control and saline control. Also, myofibroblastic cell with Ad-RLN demonstrated a 74% inhibition of fibronectin and a 52% decrease in total collagen synthesis at 48 h compared with cultures with viral control and saline control. In conclusion, the RLN gene render antifibrogenic effect on myofibroblastic cells from Dupuytren's nodule via direct inhibition of collagen synthesis not through collagenolytic pathway such as MMP-1, -13, TIMP 1, and 3. Therefore relaxin can be an alternative therapeutic strategy in initial stage of Dupuytren's disease by its antifibrogenic effect.

Original languageEnglish
Pages (from-to)515-523
Number of pages9
JournalJournal of Orthopaedic Research
Volume32
Issue number4
DOIs
Publication statusPublished - 2014 Apr

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine

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