Inflammatory osteoclastogenesis can be induced by GM-CSF and activated under TNF immunity.
In inflammatory arthritis such as RA, osteoclastic activity is severely enhanced. GM-CSF was reportedly elevated in synovial fluid, but is a strong inhibitor of osteoclastogenesis; here lies a contradiction. Our objective was to examine what type of osteoclasts generate and resorb bone with resistance to GM-CSF in an inflammatory joint. Monocyte-derived cells generated in GM-CSF were morphologically and immunophenotypically different from both the conventional DC and macrophage. They could differentiate into osteoclasts in the presence of RANKL + M-CSF, acquiring a stronger osteoclastic activity under TNF treatment. Furthermore, their differentiation was not inhibited by GM-CSF, while monocyte-derived osteoclast differentiation was completely inhibited. The resorption was suppressed by GM-CSF, and the existence of another osteoclastic pathway has been suggested. Our findings indicate another type of osteoclast exists in inflammatory arthritis.
Nomura
Koji
K
Department of Orthopaedics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
Kuroda
Shoko
S
Yoshikawa
Hideki
H
Tomita
Tetsuya
T
D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor