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• W2991073473 abstract "Objective We have previously reported that the coactivation of NF ‐κB and STAT 3 in nonimmune cells, including synovial fibroblasts, enhances the expression of NF ‐κB target genes and plays a role in chronic inflammation and rheumatoid arthritis ( RA ). This study was undertaken to examine the role of NF ‐κB activation in chondrocytes and better understand the pathogenesis of RA . Furthermore, transmembrane protein 147 ( TMEM 147) was investigated as a representative NF ‐κB activator in chondrocytes. Methods Clinical samples from RA patients were analyzed by immunohistochemistry. Specimens obtained from patients with polydactyly were used as control samples. The functional contribution of chondrocytes and TMEM 147 to arthritis was examined in several murine models of RA . In vitro experiments (quantitative polymerase chain reaction, RNA interference, immunoprecipitation, and confocal microscopy) were performed to investigate the mechanism of action of TMEM 147 in chondrocytes. Results Samples obtained from RA patients and mouse models of RA showed coactivation of NF ‐κB and STAT 3 in chondrocytes ( P < 0.001). This coactivation induced a synergistic expression of NF ‐κB targets in vitro ( P < 0.01). Chondrocyte‐specific deletion of STAT 3 significantly suppressed the development of cytokine‐induced RA ( P < 0.01). TMEM 147 was highly expressed in chondrocytes from RA patient samples and the mouse models of RA. Gene silencing of TMEM 147 or anti‐ TMEM 147 antibody treatment inhibited the cytokine‐mediated activation of NF ‐κB in vitro ( P < 0.01) and suppressed cytokine‐induced RA in vivo ( P < 0.01). Mechanistically, TMEM 147 molecules acted as scaffold proteins for the NF ‐κB complex, which included breakpoint cluster region and casein kinase 2, and enhanced NF ‐κB activity. Conclusion These results suggest that chondrocytes play a role in the development of RA via TMEM 147‐mediated NF ‐κB activation and indicate a novel therapeutic strategy for RA ." @default.
• W2991073473 created "2019-12-05" @default.
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• W2991073473 date "2020-05-02" @default.
• W2991073473 modified "2023-10-16" @default.
• W2991073473 title "Role of Chondrocytes in the Development of Rheumatoid Arthritis Via Transmembrane Protein 147–Mediated <scp>NF</scp>‐κB Activation" @default.
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• W2991073473 doi "https://doi.org/10.1002/art.41182" @default.
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