Inhibition of ERK pathway decreases the synovial hyperplasia and angiogenesis of rheumatoid arthritis rats

The purpose of this study was to explore the role and possible mechanism of inhibiting extracellular signal-regulated kinase (ERK) pathway on rheumatoid arthritis synovial hyperplasia and angiogenesis. Thirty six Sprague-Dawley rats were randomly assigned into normal group, model group, and intervention group, 12 rats in each group. The measures of enzyme-linked immunosorbent assay (ELISA), RT-PCR, Western blot, and HE immunohistochemical staining were used to examine specific indicators in this study. The levels of interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), and angiopoietin-1 (Ang-1) in the serum of model group were significantly increased (P < 0.05) compared to the normal groups. In contrast with the model group rats, the levels of IL-1 beta, TNF-alpha, and Ang-1 in the intervention group were all significantly decreased (P < 0.05). In addition, the mRNA expression of IL-1 beta. TNF-alpha, vascular endothelial growth factor (VEGF), and Ang-1 in the synovial tissue of the model group was distinctly higher than those in the normal group (P < 0.05). Simultaneously, the levels of cytokines in the intervention group were obviously decreased compared to the model group (P < 0.05). The expression of phosphorylated state of ERK1/2 (p-ERK1/2), p-JNK, and p-38 in model group rats were significantly higher than those in normal group (P < 0.05), while the expression of p-ERK1/2 in intervention group rats was evidently decreased compared to model groups (P < 0.05). Finally, the arthritis index and arthritis volume in intervention group were decreased obviously (P < 0.05). Inhibition of ERK pathway could suppress the levels of inflammatory cytokines in synovial tissue and also inhibit the proliferation of synovial tissue, and reduce angiogenesis and pannus formation in synovial membrane.