Background Endocan, previously called endothelial cell-specific molecule (ESM-1), has been studied as a pro-angiogenic factor in tumor tissues. Endocan binds CD11a/CD18 integrin (also called LFA-1 for Leukocyte Function-associated Antigen-1) on human leukocytes, consequently inhibiting its binding to ICAM-1 and preventing transendothelial migration. These physiological functions of endocan may also be involved in the angiogenesis of pannus in rheumatoid arthritic joints, which shows tumor-like growth. Here, we describe for the first time that endocan expression is increased in arthritic synovial tissues and that adiponectin is one of the important factors that increases endocan expression in synovial cells.
Objectives This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, is increased in rheumatoid arthritic tissues. In addition, we examined the contribution of adiponectin in the regulation of endocan expression in arthritic joints.
Methods Arthritic synovial tissues from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were immunostained with antibodies to endocan and VEGF. Synovial cells and human umbilical vein endothelial cells (HUVEC) were cultured and stimulated with IL-1β and/or adiponectin. The mRNA and protein levels of endocan were measured by PCR and ELISA, respectively.
Results Endocan expression was greatly increased in inflammatory sites of RA synovial tissues. In OA tissues, its expression was higher in tissues with moderate to severe inflammation than in those with mild inflammation. In vitro expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1β stimulation. Adiponectin was a more potent stimulator of endocan than was IL-1β at their respective physiological concentrations in synovial cells. Endocan silencing by siRNA transfection in synovial cells decreased in vitro cell migration and invasion.
Conclusions Adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints.
Disclosure of Interest None declared