Additionally, the knockdown of Wnt inhibitors, such as secretory frizzled-related protein-3 (sFRP-3), is associated with increased susceptibility to OA (Loughlin et al., 2004; Lories et al., 2007), and genetic variants of DKK1 are significantly associated with joint destruction in patients with rheumatoid arthritis (RA), who also have higher levels of functional serum DKK1 (Diederik et al., 2013). This evidence concerns the gene FRZB and rheumatoid arthritis.