Rheumatoid synovial endothelial cells produce macrophage colony-stimulating factor leading to osteoclastogenesis in rheumatoid arthritis.
OBJECTIVE
Periarticular osteoporosis and joint destruction are major complications in rheumatoid arthritis (RA), caused by osteoclast-mediated bone resorption. However, the mechanisms of monocyte/osteoclast maturation and role of RA endothelial cells (RAECs) in the control of osteoclastogenesis remain unclear. The present study was designed to determine the most important factors that influence monocyte accumulation and osteoclast formation among the many factors produced by RAEC.


METHODS
We analysed the expression profiles of various genes in human endothelial cells from various organs (RA synovium, umbilical vein, skin, liver sinusoid, renal glomerulus and brain) using oligonucleotide microarrays. Specifically, up-regulated gene in RAECs was assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and immunostaining of RA synovia. Migration of monocytes was assessed by the chemotactic chamber EZ-TAXIScan. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation was observed by microscopy.


RESULTS
Among many epithelial-expressed factors, macrophage colony-stimulating factor (M-CSF) gene was abundantly expressed specifically in RAECs. Genes of fibroblast growth factor-2, interleukin-6 and osteoprotegerin were also overexpressed in RAECs. Migration of monocytes and osteoclast formation in co-cultures promoted by culture supernatants of RAECs were inhibited by M-CSF neutralizing antibody.


CONCLUSIONS
M-CSF produced by RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation.
Nakano
K
K
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Okada
Y
Y
Saito
K
K
Tanikawa
R
R
Sawamukai
N
N
Sasaguri
Y
Y
Kohro
T
T
Wada
Y
Y
Kodama
T
T
Tanaka
Y
Y
D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor