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 alpha-smooth muscle actin was expressed on STRO-1+ cells.


CONCLUSIONS
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.
Rüger
Beate
B
University of Vienna, Vienna, Austria.
Giurea
Alexander
A
Wanivenhaus
Axel H
AH
Zehetgruber
Harald
H
Hollemann
David
D
Yanagida
Genya
G
Groger
Marion
M
Petzelbauer
Peter
P
Smolen
Josef S
JS
Hoecker
Paul
P
Fischer
Michael B
MB
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000235:genetics / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D023282:Nuclease Protection Assays; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D040301:Vascular Endothelial Growth Factor Receptor-2; D012260:Ribonucleases