Isozaki, T., Rabquer, B. J., Ruth, J. H., Haines, G. K., & Koch, A. E. (2013). ADAM-10 is overexpressed in rheumatoid arthritis synovial tissue and mediates angiogenesis. Arthritis and Rheumatism, 65(1), 98-108.
Objective – To examine the expression of ADAM-10 in rheumatoid arthritis (RA) synovial tissue (ST) and the role it plays in angiogenesis. Methods ADAM-10 expression was determined using immunohistology, Western blotting, and quantitative polymerase chain reaction. In order to examine the role of ADAM-10 in angiogenesis, we performed in vitro Matrigel tube formation and chemotaxis assays using human microvascular endothelial cells (HMVECs) transfected with control or ADAM-10 small interfering RNA (siRNA). To determine whether ADAM-10 plays a role in angiogenesis in the context of RA, we performed Matrigel assays using a coculture system of HMVECs and RA synovial fibroblasts.
Results – Endothelial cells and lining cells within RA ST expressed high levels of ADAM-10 compared with cells within osteoarthritis ST and normal ST. ADAM-10 expression was significantly elevated at the protein and messenger RNA levels in HMVECs and RA synovial fibroblasts stimulated with proinflammatory mediators compared with unstimulated cells. ADAM-10 siRNAtreated HMVECs had decreased endothelial cell tube formation and migration compared with control siRNAtreated HMVECs. In addition, ADAM-10 siRNAtreated HMVECs from the RA synovial fibroblast coculture system had decreased endothelial cell tube formation compared with control siRNAtreated HMVECs.
Conclusion – These data show that ADAM-10 is overexpressed in RA and suggest that ADAM-10 may play a role in RA angiogenesis. ADAM-10 may be a potential therapeutic target in inflammatory angiogenic diseases such as RA.