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31 March 2016 : Animal Research  

Inhibition of GSK-3β Alleviates Collagen II-Induced Rheumatoid Arthritis in Rats

Haiyan ZhouE, Jun LiuBD, Jiashun ZengB, Bailong HuC, Xiuyi FangBCD, Long LiABCDE

DOI: 10.12659/MSM.897739

Med Sci Monit 2016; 22:1047-1052

Abstract

BACKGROUND: Glycogen synthase kinase-3β (GSK-3β) inhibitor is a serine/threonine kinase with an inhibitory role in glycogen synthesis, which is essential in inflammatory and immunological diseases. The purpose of our study was to determine if TDZD-8 can alleviate collagen II-induced rheumatoid arthritis in rats.

MATERIAL AND METHODS: Twenty collagen II-induced rheumatoid arthritis rats were treated with selective GSK-3β inhibitor. The effects of GSK-3β inhibition on collagen II-induced rheumatoid arthritis in the rats were evaluated by paw edema, histological examination of arthritic synovium, radiographic examination of knee joint, and the level of inflammation mediators such as prostaglandin E2, 5-hydroxytryptamin, and histamine. The level of cytokines such as IL-6, IL-12, IL-10, and TNF-α, was examined by Elisa.

RESULTS: GSK-3β inhibitor significantly reduced the development of rheumatoid arthritis in rats. The levels of inflammation mediators such as prostaglandin E2, 5-hydroxytryptamin, and histamine were decreased in the TDZD-8 group. Serum levels of IL-6, IL-12, and TNF-α were significantly reduced in the TDZD-8 group compared with the RA group.

CONCLUSIONS: Treatment with GSK-3β inhibitor suppressed inflammatory response in RA rats. These findings suggest that the inhibition of GSK-3β can be an effective treatment for RA.

Keywords: Arthritis, Rheumatoid - pathology, Cattle, Collagen Type II, Cytokines - metabolism, Dinoprostone - metabolism, Glycogen Synthase Kinase 3 beta - metabolism, Histamine - metabolism, Joints - pathology, Protein Kinase Inhibitors - therapeutic use, Rats, Wistar, Serotonin - metabolism, Synovial Membrane - pathology, Thiadiazoles - therapeutic use

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750