阿格里坎
软骨
骨关节炎
一氧化氮
软骨细胞
II型胶原
一氧化氮合酶
化学
医学
解剖
病理
内科学
关节软骨
替代医学
作者
Masanori Yorimitsu,Keiichiro Nishida,Akira Shimizu,Hideyuki Doi,Shinichi Miyazawa,Takamitsu Komiyama,Y. Nasu,Aki Yoshida,Shohei Watanabe,T. Ozaki
标识
DOI:10.1016/j.joca.2007.11.006
摘要
ObjectiveTo investigate the in vitro and in vivo effects of interleukin (IL)-4 on mechanical stress-induced nitric oxide (NO) expression by chondrocytes, and destruction of cartilage and NO production in an instability-induced osteoarthritis (OA) model in rat knee joints, respectively.Materials and methodsCyclic tensile stress (CTS; 0.5 Hz and 7% elongation) was applied to cultured normal rat chondrocytes with or without pre-incubation with recombinant rat IL-4 (rrIL-4). Inducible NO synthase (iNOS) mRNA expression and NO production were examined with real-time polymerase chain reaction and the Griess reaction, respectively. OA was induced in rat knee joints by transection of the anterior cruciate and medial collateral ligaments and resection of the medial meniscus. rrIL-4 (10, 50, and 100 ng/joint/day) was injected intra-articularly, and knee joint samples were collected 2, 4, and 6 weeks after surgery. Cartilage destruction was evaluated by the modified Mankin score and Osteoarthritis Research Society International scoring system on paraffin-embedded sections stained with safranin O. Cleavage of aggrecan and NO production were examined by immunohistochemistry for aggrecan neoepitope (NITEGE) and of nitrotyrosine (NT), respectively.ResultsrrIL-4 down-regulated CTS-induced iNOS mRNA expression and NO production by chondrocytes. The intra-articular injection of rrIL-4 gave rise to a limited, but significant amelioration of cartilage destruction, prevention of loss of aggrecan, and decrease in the number of NT-positive chondrocytes, an effect that was not dose-dependent.ConclusionThe present study suggests that IL-4 may exert chondroprotective properties against mechanical stress-induced cartilage destruction, at least in part, by inhibiting NO production by chondrocytes.
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