A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis.
Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheumatoid arthritis in 2-3 weeks in the presence of 1,25(OH)2vitaminD3 without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co-culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phenotypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin receptors, receptors for human calcitonin and the ability to resorb bone. These results indicate that synovial macrophages are capable of differentiating into osteoclasts in the presence of rheumatoid synovial fibroblasts which can support differentiation of monocytes/ macrophages, implicating that osteoclasts generated within the synovial membrane are probably involved in bone destruction in rheumatoid arthritis.
Takayanagi
H
H
Department of Orthopaedics, University of Tokyo, Japan.
Oda
H
H
Yamamoto
S
S
Kawaguchi
H
H
Tanaka
S
S
Nishikawa
T
T
Koshihara
Y
Y
D000135:Acid Phosphatase / Q000096:biosynthesis; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D001862:Bone Resorption / Q000503:physiopathology*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D018003:Receptors, Calcitonin / Q000096:biosynthesis; D019030:Receptors, Vitronectin / Q000096:biosynthesis; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013583:Synovial Membrane / Q000473:pathology / Q000503:physiopathology*; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
D007527:Isoenzymes; D018003:Receptors, Calcitonin; D019030:Receptors, Vitronectin; D016173:Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol