Midkine as a molecular target: comparison of effects of chondroitin sulfate E and siRNA.

Midkine as a molecular target: comparison of effects of chondroitin sulfate E and siRNA.
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DOI:
10.1016/j.bbrc.2006.10.123
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发表时间:
2006-12
影响因子:
3.1
通讯作者:
Hideki Yamamoto;H. Muramatsu;T. Nakanishi;Yukikazu Natori;S. Sakuma;N. Ishiguro;T. Muramatsu
Hideki Yamamoto;H. Muramatsu;T. Nakanishi;Yukikazu Natori;S. Sakuma;N. Ishiguro;T. Muramatsu
中科院分区:
生物学4区
文献类型:
--
作者:
Hideki Yamamoto;H. Muramatsu;T. Nakanishi;Yukikazu Natori;S. Sakuma;N. Ishiguro;T. Muramatsu

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腹腔注射硫酸软骨素 E 可以抑制抗体诱导的关节炎(一种类风湿性关节炎模型)的发展,而 4-硫酸软骨素则没有效果。硫酸软骨素 E 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 的靶标之一是中期因子,一种肝素结合生长因子或细胞因子。事实上,中期因子的嵌合型 siRNA 抑制了抗体诱导的关节炎的发展以及大网膜与受损腹壁的粘附。这些结果表明中期因子作为治疗或预防类风湿性关节炎和手术后粘连的分子靶点的重要性,以及硫酸软骨素E在体内抑制中期因子的效用。
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.