Midkine as a molecular target: comparison of effects of chondroitin sulfate E and siRNA.
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.
Yamamoto
Hideki
H
Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Muramatsu
Hisako
H
Nakanishi
Takashi
T
Natori
Yukikazu
Y
Sakuma
Sadatoshi
S
Ishiguro
Naoki
N
Muramatsu
Takashi
T
D000818:Animals; D000906:Antibodies / Q000633:toxicity; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002809:Chondroitin Sulfates / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D000078792:Midkine; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000627:therapeutic use*
D000906:Antibodies; D016207:Cytokines; D034741:RNA, Small Interfering; D000078792:Midkine; D002809:Chondroitin Sulfates