Correlation Between NF-kappaB (NF-κB), Receptor Activator Of NFkappaB Ligand (RANKL) And Matrix Metalloproteinase-9 (MMP-9) Expression In Synovium Of Collagen-induced Arthritis Rats

Objectives: To investigate the expression of NF-kappaB(NF-κB), receptor activator of NF-kappaB ligand (RANKL), matrix metalloproteinase-9 ( MMP-9 ) in synovium of collagen-induced arthritis rats (CIA) at various time points and the relationship with interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), in order to realize the mechanism of them in CIA and provide new method of diagnosis and therapy for rheumatoid arthritis(RA).Methods: Forty-two male Wistar rats were randomly divided into 2 groups(each 21), namely the model control group and the normal control group. CollagenⅡ(CⅡ) and complete Freund's adjuvant were used to induce experimental arthritis(CIA) contrast with isotonic Na chloride. Synovium expression of NF-κB, RANKL, MMP-9 were obtained for immunohistochemical analyses and plasma contents of IL-1β, TNF-αwere determined for radioimmunoassay(RIA). These cytokines were assayed simultaneously at various time points and changes between arthritis index(AI), histological scores and these cytokines were observed along the time course. The expression of RANKL, MMP-9, NF-κB and plasma contents of IL-1β, TNF-αwere assayed by factorial analysis at different time points. The correlations between those of NF-κB, RANKL, MMP-9, IL-1βand TNF-α, AI, histological scores and these cytokines were studied with linear correlation analysis and rank correlation analysis respectively.Results: With the time lasting and synovium thickened, the histological scores and arthritis index rose gradually as well as those of NF-κB, RANKL, MMP-9, TNF-αand IL-1βrose too. These cytokines are significantly higher in CIA group than control(p<0.01). AI and the histological scores correlated with NF-κB, MMP-9 expression levels (p<0.05), and RANKL rose, but showed no significant difference(p>0.05) and these cytokines had a positive correlation(p<0.05). NF-κB, RANKL, MMP-9 with IL-1β, TNF-αhad a positive correlation(p<0.05).Conclusion: The expression levels of NF-κB, RANKL, MMP-9 in synovium and plasma contents of IL-1β, TNF-αare significantly higher in CIA group than control. The expression of RANKL, MMP-9 and NF-κB in synovium of collagen-induced arthritis rats have intimate correlation with IL-1βand TNF-α. Those cytokines are possible mutual influence and promoting result to positive feedback mechanism that made important function of progress in CIA and they may play the key role of pathogenesis, development and joint destruction in RA.