2018 Volume 78 Issue 2 Pages 117-125
A disintegrin and metalloprotease 15 （ADAM-15） is expressed in several malignancies. However, the relationship between ADAM-15 and rheumatoid arthritis （RA） is still unclear. In this study, we investigated the role of ADAM-15 in RA angiogenesis. RA and normal （NL） serum, and in the same way, RA and osteoarthritis （OA） synovial fluids were obtained from RA patients and control patients. ADAM-15 expression was determined in serum and synovial fluid from RA and NL using ELISA. To determine ADAM-15 expression in RA synovial tissues, immunohistochemistry was performed. To determine the role of ADAM-15 in RA, cytokines in ADAM-15 siRNA-treated human umbilical vein endothelial cell （HUVEC） was measured. Then, in order to confirm the role of angiogenesis, we did Matrigel assays in vitro. Finally, to determine whether ADAM-15 mediates adhesion to ECs, we performed in vitro adhesion assays. ADAM-15 in RA serum was significantly higher compared with NL and it was significantly higher in RA compared with OA synovial fluids. ADAM-15 is expressed on the endothelial cell in RA synovial tissues. ENA-78/CXCL5 and ICAM-1 in TNF-α-stimulated ADAM-15 siRNA-transfected HUVEC conditioned medium were decreased compared with in TNF-α-stimulated control siRNA-transfected HUVEC conditioned medium. ADAM-15 siRNA-treated HUVECs had a decreased EC line and tube formed in response to RA synovial fluids compared with non-treated HUVECs. Adhesion index of ADAM-15 siRNA transfected HUVECs was significantly decreased compared with adhesion index of control siRNA transfected HUVECs. These data show ADAM-15 plays a role in RA angiogenesis, suggesting that ADAM-15 may be a potential target in inflammatory diseases such as RA.
