Significant additive interactions were observed between DKK1: rs1896368 and LRP5: rs3736228, relative excess risk due to interaction (RERI) = 0.40, 95% CI = 0.08 - 0.71; attributable proportion due to interaction (AP) = 51%, 95% CI = 0.07 - 0.94, DKK1: rs1569198 and LRP5: rs3736228 (RERI = 0.49, 95% CI = 0.12 - 0.86; AP = 49%, 95% CI = 0.17 - 0.82), LRP5: rs3736228 and SOST: rs4792909 (RERI = 0.33, 95% CI = 0.002 - 0.65; AP = 41%, 95% CI = 0.01 - 0.81) in the dominant model.<b>Conclusions:</b> Our research implies a potential gene-gene interaction, thus revealing the importance of the Wnt/β-catenin signalling pathway for understanding the genetic architecture of AS.
The expression of miR-29a, DKK-1 and β-catenin in normal and AS tissues were detected with real-time polymerase chain reaction (RT-PCR) and western blotting.
Although serum DKK-1 concentration was not significantly different in AS vs. healthy controls, it may be used as a biomarker of inflammation and radiographic damage in AS.
Mechanism studies further revealed that loss of DKK1 partly reversed the effect of miR-146a inhibitor on cell proliferation, apoptosis and osteogenic potential in AS fibroblasts.
Dkk-1 levels were significantly (P<0.05) higher in AS patients with elevated ESR and CRP and no syndesmophytes, and were significantly (P<0.001) correlated with sclerostin levels (r=0.592).
At the baseline and 2-year follow-up, serum adiponectin, leptin, resistin, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and Dickkopf-1(DKK-1) levels were measured in AS patients using enzyme-linked immunosorbent assays; these measurements were only performed at the baseline for healthy controls.
Furthermore, Dkk-1 concentrations were significantly higher along a spectrum of increasing axial arthritis; Dkk-1 concentrations were higher in AS compared with PsSpA (OR<sub>adj</sub> 1.18 per ng/mL increase; p = 0.02).
Therefore, we concluded that the beneficial role of <i>Chrysanthemum indicum</i> in AS is manifested through downregulating oxidative stress, inhibiting inflammatory mediators and NF-<i>κ</i>B, and increasing DKK-1 and SOST levels.
Recent evidence suggests that new bone formation in AS may be due to upregulation of Wnt signaling in the osteoblastic pathway secondary to low serum Dickkopf homolog 1 (Dkk-1) levels.