Endothelial Precursor Cells in the Synovial Tissue of Patients With Rheumatoid Arthritis and Osteoarthritis

Objective. To find evidence for the presence of endothelial precursor cells, which can induce new vessel formation, in the synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Methods. Precursor cells in the synovial tissue of 18 RA patients and 15 OA patients were identified by immunohistochemistry, morphometric analysis, and confocal laser scanning microscopy using the following phenotype markers: CD31, CD34, STRO-1, CD133, vascular endothelial growth factor receptor 2 (VEGFR-2), and CXCR4. The presence of CD31, CD34, CD133, VEGFR-2, and CXCR4 messenger RNA in the synovial tissue was determined by reverse transcriptase– polymerase chain reaction, and the message for CXCR4 was quantified by an RNase protection assay. Results. A population of cells that expressed CD34 on their surface but lacked the endothelial cell marker CD31 was found in the synovial tissue of RA and OA patients. CD34,CD31 cells were detected in close proximity to STRO-1 and CD133 cells, forming cell clusters in the sublining area of the synovial membrane. Within these cell clusters, CD34,CD31 precursor cells were located on the inside surrounded by STRO-1 cells and with CD133 cells on the outside. CD34 precursor cells in the cell layer expressed high levels of the chemokine receptor CXCR4, while VEGFR-2 was expressed on CD34 and CD133 cells, and -smooth muscle actin was expressed on STRO-1 cells. Conclusion. The presence of endothelial precursor cells in the synovial tissue of RA and OA patients provides evidence for vasculogenesis induced by precursor cells that arise in situ or from circulating progenitors. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, characterized by destruction of multiple joints in which the articular cartilage and bone are destroyed by proliferative synovitis. The synovial lesion is formed by proliferation of synovial lining cells, thickening of the synovial membrane with villous projections, dense infiltration of the synovia with lymphocytes, macrophages, dendritic cells, and plasma cells,