ABSTRACT
OBJECTIVES: 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.
Subject(s)
Arthritis, Rheumatoid/metabolism , Macrophage Colony-Stimulating Factor/biosynthesis , Osteoclasts/pathology , Synovial Membrane/metabolism , Arthritis, Rheumatoid/pathology , Cell Differentiation/drug effects , Cells, Cultured , Chemotaxis, Leukocyte/drug effects , Coculture Techniques , Endothelial Cells/metabolism , Endothelial Cells/pathology , Enzyme-Linked Immunosorbent Assay/methods , Gene Expression , Humans , Macrophage Colony-Stimulating Factor/genetics , Macrophage Colony-Stimulating Factor/pharmacology , Monocytes/drug effects , Monocytes/physiology , Oligonucleotide Array Sequence Analysis/methods , Osteoclasts/drug effects , RNA, Messenger/genetics , Synovial Membrane/pathologyABSTRACT
This 42-year-old man experienced a sudden onset of occipital headache. Neurological examination revealed a moderately disturbed consciousness and a moderate left hemiparesis. CT scan disclosed a hugh hematoma in the right temporo parietal lobe without intraventricular hemorrhage. A cerebral angiography demonstrated typical findings of moyamoya disease and a small saccular aneurysm at the peripheral portion of the right anterior choroidal artery, which was dilated at the collateral circulation to the parietal lobe. The hematoma was removed at once by a craniotomy. He became alert but mild hemiparesis persisted. MRI disclosed a small signal-void lesion lateral to the trigone of the right lateral ventricle. The angiography repeated three weeks after the removal of the hematoma showed the unchanged size of the aneurysm. Direct surgery for the aneurysm was performed via the right parietal transcortical approach. The aneurysm was reached under the guidance of the intraoperative angiography. Trapping of the parent artery and the excision of the aneurysm were performed. On the basis of the presence of an internal elastic lamina at the neck of the aneurysm, the surgical specimen was histologically verified to be a true aneurysm. Since the collateral circulation was well preserved during surgery, no worsening of the neurological manifestation was observed. In view of the unfavorable prognosis for a moyamoya patient with this type of the aneurysm, which often results in a massive ventricular or intracerebral hemorrhage, surgery directed to the aneurysm itself should be considered.
