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• W2014540204 abstract "Abstract Objective The mechanisms of osteoclast maturation and the role of rheumatoid arthritis (RA) synovial fibroblasts in the control of osteoclastogenesis remain unclear. The purpose of this study was to determine the humoral factors that influence osteoclast differentiation resulting from mutual interactions between osteoclast progenitor cells and synovial fibroblasts. Methods The cloned mouse macrophage cell line RAW 264.7 or isolated human CD14+ monocytes were cocultured with RA or osteoarthritis (OA) synovial fibroblasts in the presence of RANKL. Osteoclasts were visualized by staining for tartrate‐resistant acid phosphatase (TRAP), and their functions were evaluated by bone resorption assay. Transforming growth factor β (TGFβ) and osteoprotegerin (OPG) levels were measured by enzyme‐linked immunosorbent assay. Expression of pSmad2 and Smad7 was analyzed by Western blotting. Results RANKL‐mediated osteoclast formation was observed in cocultures of RAW cells with RA synovial cells, but not with OA synovial cells. This formation was inhibited by TGFβ receptor kinase inhibitor or neutralizing TGFβ antibody. Human CD14+ monocytes showed the same results with RAW 264.7, and bone resorption activity was consistent with osteoclast formation. RA synovial fibroblasts produced TGFβ in response to cell–cell contact with RAW cells in a RANKL‐dependent manner. TGFβ reduced OPG production by RA synovial fibroblasts, but dose‐dependently increased OPG secretion in OA synovial fibroblasts. TGFβ decreased the expression of pSmad2 and increased the expression of Smad7 in RA synovial fibroblasts, but not OA synovial fibroblasts. Conclusion Suppression of OPG production by down‐regulation of TGFβ/Smad2 signaling may contribute to RANKL‐mediated osteoclastogenesis from RA synovial fibroblasts." @default.
• W2014540204 created "2016-06-24" @default.
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• W2014540204 date "2008-10-30" @default.
• W2014540204 modified "2023-10-16" @default.
• W2014540204 title "Coculture of osteoclast precursors with rheumatoid synovial fibroblasts induces osteoclastogenesis via transforming growth factor β-mediated down-regulation of osteoprotegerin" @default.
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• W2014540204 doi "https://doi.org/10.1002/art.23971" @default.
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