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Dickkopf-1 induces migration in fibroblast-like synoviocytes

  • Author(s): Dieffenbach, Bryan V.
  • et al.
Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting joint tissues. Disease is characterized by synovial hyperproliferation and joint invasion, severe inflammatory cell influx and matrix destruction. Serum levels of the wnt antagonist, Dickkopf-1, are increased in diseased patients and have been described to affect bone homeostasis in affected joints. Here we introduce an additional role for Dickkopf-1, the induction of migration in fibroblast-like synoviocytes (FLS) in vitro. Our results show that Wnt5a and surprisingly, DKK1 induce migration in wound edge C57Bl/6 FLS. Wnt5a has previously been demonstrated to induce migration in a JNK dependent manner whereas DKK1 has been implicated in both induction and inhibition of migratory behavior. Migrating FLS exhibit activation of JNK1 and JNK2, and the absence of either isoform limits the induction of synoviocyte migration, indicating that JNK is required for FLS migration. However, Dickkopf-1 treatment of JNK1 deficient FLS was able to induce migration in wound edge cells, while JNK2 deficient FLS were refractory. These findings suggest that the Wnt signaling pathways contribute to migration in FLS in vitro. Elevated signaling through Wnt- affiliated molecules may account for the aberrant migratory behavior of synovial cells in rheumatoid arthritis patients

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