24 January 2020 : Laboratory Research
NF-κB Phosphorylation Inhibition Prevents Articular Cartilage Degradation in Osteoarthritis Rats via 2-AminoquinolineJinlong He1BCDE, Shicheng Zheng1AEF*
Med Sci Monit 2020; 26:e920346
BACKGROUND: Osteoarthritis is a chronic degenerative disease of the joints that is common in older people worldwide. The characteristic features of osteoarthritis include cartilage degradation, synovitis, and remodelling of subchondral bone. The present study investigated the effect of 2-aminoquinoline on knee articular cartilage degradation in an osteoarthritis rat model.
MATERIAL AND METHODS: The rat model of osteoarthritis was established in Wistar rats by intra-articular injection of monosodium iodoacetate. The rats were randomly divided into 6 groups of 10 rats each: a normal control group, an untreated group, and 4 (5, 10, 15 and 20 mg/kg) treatment groups. The rats in treatment groups received 5, 10, 15, or 20 mg/kg doses of 2-aminoquinoline on day 2 of monosodium iodoacetate injection.
RESULTS: The 2-aminoquinoline treatment of monosodium iodoacetate-injected rats markedly decreased weight-bearing asymmetry, inhibited edema formation, and improved paw withdrawal thresholds. The expression of inflammatory cytokines was markedly higher in the osteoarthritis rats. Treatment with 2-aminoquinoline led to a significant reduction in inflammatory cytokine expression in osteoarthritis rats in a dose-dependent manner. In osteoarthritis rats, the expressions of prostaglandin E2 (PGE2), matrix metalloproteinase-13 (MMP-13), and substance P were also higher in comparison to the control group. The 2-aminoquinoline treatment supressed PGE2, MMP-13, and substance P levels in osteoarthritis rats. Moreover, the expression of phosphorylated nuclear factor kappaB (p-NF-κB) was markedly higher in the untreated rats. However, activation of NF-κB was downregulated in the osteoarthritis rats by treatment with 2-aminoquinoline.
CONCLUSIONS: The present study demonstrated that 2-aminoquinoline prevents articular cartilage damage in osteoarthritis rats through inhibition of inflammatory factors and downregulation of NF-κB activation, suggesting that 2-aminoquinoline would be effective in treatment of osteoarthritis.
Keywords: angioedema, Cytokines, synovitis, Aminoquinolines, Cartilage, Articular, Dinoprostone, Edema, Extremities, Joints, Matrix Metalloproteinase 13, Osteoarthritis, Phosphorylation, Rats, Wistar, Receptors, Purinergic P2X7, substance P
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