Serum Levels And Clinical Significances Of DKK-1 In Patients With Rheumatoid Arthritis

Background and objectiveRheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease. The pathological characteristic of RA includes synovial hyperplasia and inflammation, pannus formation, in the end.bone erosion, cartilage loss and joint destruction.If left untreated, it would lead to joint damage and disability. The pathogenesis of RA involved a variety of signal transduction pathways, there are many cytokines, enzymes and adhesion molecules interact in the process and regulate the pathophysiological process of RA.Any of them can impact on the pathogenesis of RA.Wnt signaling pathway is the most important and classical in cell signaling pathway,regulated cell growth,development, differentiation and tissue repair. Recent study suggested that canonical Wnt signaling pathway play an important role in mediating the alterations of joint tissue turnover associated with rheumatoid arthritis. Dickkopf-1,a secreted inhibitor of the canonical Wnt signaling pathway is a master regulator of joint remodeling. As a result,we detecting the serum level of DKK-1 in RA patients,to evaluate the relationship between DKK-1 level and clinical index and to explore the role of DKK-1 in the pathogenesis of RA. Methods:(1)82 RA patients (48 early RA,34 late RA),46 SpA patients and 48 normal controls were included in this study, and the serum were collected at baseline and assessed by enzyme-linked immunosorbent assay (ELISA). To investigated the relation between serum levels of DKK-1 in RA patients and clinic observed index.The core indicators of RA including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, disease activity score (DAS28) were all documented. (2) 48 early RA patients were divided into 2 groups, one receiving therapy with etanercept combined with MTX and the other with MTX alone.After 12 week follow-up, serum were also collected to detect DKK-1 levels.Simultaneously, to observe the changes of clinic index between at baseline and after therapyResults(1)The levels of DKK-1 in early RA group and SpA group were higher than normal controls group,but without significant difference (P>0.05). No significant difference was detected between early RA and SpA group. The levels of DKK-1 in late RA group were higher than that in early RA group, with significant statistical difference(P<0.05);(2)Correlations between DKK-1 levels and ESR,CRP, anti-CCP, RF, DAS28 scores were detected in all the RA patients (P<0.05), but not in the early RA group (P>0.05); (3)Serum DKK-1 levels decreased in the early RA group receiving eternercept combined with MTX treatment (3003.40±638.13pg/ml versus 2136.16±353.52pg/ml,P<0.05), but there is no significant decrease in the early RA group receiving MTX treatment(2821.01±632.43pg/ml versus 2803.62±574.31pg/ml, P>0.05).Conclusion1.The levels of DKK-1 was no difference in early RA group,SpA group and normal controls group,but the levels of DKK-1 increased in late RA group. Serum DKK-1 levels correlate with bone erosion.2.There were no correlations between serum DKK-1 levels in early RA group and ESR, CRP, anti-CCP, RF, DAS28 score. DKK-1 participates in the pathogenesis independently. 3.Anti-TNF-αtherapy downregulates DKK-1 expression in early RA. The protective effect of the DKK-1 executive by inhibit DKK-1 expression.