Protective Role Of Smad7 In Rheumatoid Arthritis

Objective:To explore the role of Smad7 in rhuematoid arthritis (RA) and the possible mechanisms. Method:This study was investigated in the collagenⅡ-induced arthritis(CIA) model induced in wild-type (WT) and Smad7 gene knockout mice.44 mice were divided into six groups, including Smad7-WT/KO normal group(n=6), Smad7-WT/KO CIA model group(n=8), Smad7-WT/KO control group (n=8). The observations of the mice genernal situation、pathology and the result of IHC、Elisa and real-time PCR were compared. Result:We found that CIA mice deficient for Smad7 developed more severe arhritis than the mice in the normal and control groups as evidenced by a significant increase in joint swelling, synovial hyperplasia、articular cartilage damaged, and joint inflammation(CD3、F4/80、TNFα、MCP-1、IL-1、T-bet、IL-6、RORγt、IL-17) and TGF-β1/NF-κB signalling pathway (TGF-β、P-Smad2/3、P-P65) activation showed by IHC and RT-PCR, and serum IL-17A and anti-collagengⅡantibody(IgG、IgG1、IgG2a) significantly elevated by Elisa. Conclusion:The absence of Smad7 aggravates the arthritis, which may be related to the reduction of TGF-βand NF-κB inhibition by Smad7, increasing the NF-κB/TGF-β1 signaling pathway, and promoting Th17 differentiation, leading to immune dysfunction and inflammatory response increased.