Suppression of chondrocyte apoptosis in the osteoarthritis by interleukin-1Ra ex vivo gene therapy / 中华风湿病学杂志

ABSTRACT

Objective To explore suppression of chondrocyte apoptosis by IL-1Ra gene transfer to the knees of experimental osteoarthritis (OA).Method ①Thirty New Zealand white rabbits were divided into 3 groups,partial synovectomy of the left knee had been done.Synovial fibroblasts (SF) were isolated and cultured.②Fibroblasts from each rabbit were transduced by using the retrovirus with either IL-1Ra gene (group 3) or marker gene to (group2) in vitro.③ OA was induced in right knee of rabbits by anterior cruciate ligament transection (ACLT).④ The autologous cells transduced with IL-1Ra gene or marker gene were injected into the right knee of group 3 or 2.⑤At the second week and at the forth week,IL-1Ra level in SF was determined by ELISA.⑥Cartilage section were stained for checking histologic changes and chondrocyte apoptosis were determined using TUNEL method.Results The IL-1Ra level in the SF of group 3 were (20.6?1.8)ng/ml and (4.82?0.52)ng/ml after 2 and 4 weeks,after gene delivered respectively,and the IL-1Ra level in the group 2 and group 1 were very lowat both 2 and 4 weeks.Approximately 40% of chondrocytes underwent apoptosis in group 2,whereas apoptosis were inhibited in group 3,only 18% of chondrocytes underwent apoptosis,and 2%~5% of chondrocytes underwent apoptosis in normal joint.Conclusion This study showes that a local increase IL-1Ra level in OA keen joints by intraartilcular injection of IL-1Ra gene transduced synovial cells can suppress articular cartilage chondrocyte apoptosis.