Receptor Protein XXXX Phosphatase a-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of @entity625 in @entity19 .

@entity625 @entity19640 @entity146 @entity2667 @entity19 @entity5 @entity39 @entity8264 @entity10440 @entity26509 @entity4149 @entity309
OBJECTIVE: During @entity309 ( @entity309 ), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the extracellular matrix of the joint. The @entity8264 ( @entity8264 ) signaling pathway is emerging as a contributor to the anomalous behavior of @entity309 FLS. The receptor protein @entity4149 phosphatase a (RPTPa), which is encoded by the @entity26509 gene, is a key promoter of @entity8264 signaling. The aim of this study was to investigate whether RPTPa mediates FLS @entity146 and @entity309 pathogenesis. METHODS: Through RPTPa knockdown, we assessed FLS gene expression by quantitative polymerase chain reaction analysis and enzyme-linked immunosorbent assay, invasion and migration by Transwell assays, survival by @entity10440 and @entity2667 staining, adhesion and spreading by immunofluorescence microscopy, and activation of signaling pathways by Western blotting of FLS lysates. @entity625 development was examined in RPTPa-knockout (KO) @entity19 using the K/BxN serum-transfer model. The contribution of radiosensitive and radioresistant cells to disease was evaluated by reciprocal bone marrow transplantation. RESULTS: RPTPa was enriched in the @entity309 synovial lining. RPTPa knockdown impaired @entity309 FLS survival, spreading, migration, invasiveness, and responsiveness to platelet-derived growth factor, @entity5 @entity39 factor, and interleukin-1 stimulation. These phenotypes correlated with increased phosphorylation of @entity19640 on inhibitory Y(527) and decreased phosphorylation of @entity8264 on stimulatory Y(397) . Treatment of @entity309 FLS with an inhibitor of @entity8264 phenocopied the knockdown of RPTPa. RPTPa-KO @entity19 were protected from @entity625 development, which was due to radioresistant cells. CONCLUSION: By regulating the phosphorylation of @entity19640 and @entity8264 , RPTPa mediates proinflammatory and proinvasive signaling in @entity309 FLS, correlating with the promotion of disease in an FLS-dependent model of @entity309 .
