Functionally, an aberrant expression of Wnt signaling components has been implicated in promotion of cell growth and differentiation [46]. In vitro studies have shown that fibroblast-like synoviocytes (FLS) from patients persistently expressed high levels of both Wnt5a and Fzd5, suggesting that an activation of noncanonical Wnt5a/Fzd5 signaling may contribute to the activated state of FLS in RA, despite the fact that the constitutive activation of Wnt/Fzd signaling in RA was independent of an inflammatory environment [46, 92]. This evidence concerns the gene FZD5 and rheumatoid arthritis.