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NF-κB Phosphorylation Inhibition Prevents Articular Cartilage Degradation in Osteoarthritis Rats via 2-Aminoquinoline.

Abstract：

: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-kappaB) was markedly higher in the untreated rats. However, activation of NF-kappaB 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-kappaB activation, suggesting that 2-aminoquinoline would be effective in treatment of osteoarthritis.

journal_name

Med Sci Monit

journal_title

Medical science monitor : international medical journal of experimental and clinical research

authors

He J,Zheng S

doi

10.12659/MSM.920346

subject

Has Abstract

pub_date

2020-01-24 00:00:00

pages

e920346

eissn

1234-1010

issn

1643-3750

pii

920346

journal_volume

26

pub_type

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