Yamamoto Hideki, Muramatsu Hisako, Nakanishi Takashi, Natori Yukikazu, Sakuma Sadatoshi, Ishiguro Naoki, Muramatsu Takashi
Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):915-9. doi: 10.1016/j.bbrc.2006.10.123. Epub 2006 Nov 2.
Intraperitoneally administered chondroitin sulfate E inhibited the development of antibody-induced arthritis, a model of rheumatoid arthritis, while chondroitin 4-sulfate showed no effects. Chondroitin sulfate E inhibited in vitro differentiation of osteoclasts, which play key roles in the etiology of rheumatoid arthritis. One of the targets of chondroitin sulfate E is midkine, a heparin-binding growth factor or cytokine. Indeed, a chimeric-type siRNA for midkine inhibited the development of antibody-induced arthritis and adhesion of the omentum to the injured abdominal wall. These results indicate the significance of midkine as a molecular target to treat or prevent rheumatoid arthritis and adhesion after surgery, and the utility of chondroitin sulfate E to inhibit midkine in vivo.
腹腔注射硫酸软骨素E可抑制抗体诱导性关节炎（类风湿性关节炎模型）的发展，而硫酸软骨素4 - 硫酸酯则无此作用。硫酸软骨素E可抑制破骨细胞的体外分化，破骨细胞在类风湿性关节炎的病因学中起关键作用。硫酸软骨素E的一个靶点是中期因子，一种肝素结合生长因子或细胞因子。事实上，针对中期因子的嵌合型小干扰RNA可抑制抗体诱导性关节炎的发展以及大网膜与受伤腹壁的粘连。这些结果表明中期因子作为治疗或预防类风湿性关节炎及术后粘连的分子靶点具有重要意义，以及硫酸软骨素E在体内抑制中期因子的效用。
