The Expressions of Dickkopf-Related Protein 1 and Frizzled-Related Protein Are Negatively Correlated to Local Inflammation and Osteoarthritis Severity

Objective. To investigate the presence of WNT antagonists Dickkopf-related protein 1 (DKK1), Frizzled-related protein (FRZB) and BMP antagonist Gremlin 1 (GREM1) in synovial fluid (SF) and serum, respectively, from end-stage knee osteoarthritis (OA) patients, and correlate their expression with other markers of OA. Design. In a cross-sectional study, SF and serum were collected from OA patients (n = 132). The concentrations of DKK1, FRZB and GREM1 in SF and serum were determined using immunoassays. Correlation measurements were performed between groups and previously assessed disease markers, such as synovium nitric oxide (NO), inerleukin-1 beta (IL1 beta), tumor necrosis factor-alpha (TNF alpha), and prostaglandin E2 (PGE2). Results. The OA patients with the celecoxib treatment till surgery have higher median SF FRZB values compared with the control (no treatment); the celecoxib 3-days before surgery stopped treatment group has higher median serum FRZB values than the control and the naproxen treatment group. The combinational analysis of SF DKK1 and SF FRZB negatively correlated with macroscopic cartilage scores and histological synovium scores in OA patients. The expression of DKK1 and FRZB in SF showed the same expression trend as their expression in serum. Furthermore, the SF concentration of DKK1 was positively correlated with FRZB in both SF and serum. In contrast, it was negatively correlated with synovium NO and IL1 beta. SF FRZB was negatively correlated with synovium NO, IL1 beta cartilage PGE2, and age. Conclusions. Our findings suggest DKK1 and FRZB were negatively correlated with OA severity and multiple proinflammatory cytokines. Our data indicate that DKK1 and FRZB can be joint disease-specific biomarkers.