Association between serum and synovial fluid Dickkopf-1 levels with radiographic severity in primary knee osteoarthritis patients.

Abstract

Primary knee osteoarthritis (OA) contributes to disability among middle-aged and elderly people. Dickkopf-1 (Dkk-1) and sclerostin are inhibitors of Wnt/β-catenin signaling pathway implicated in regulation of cartilage homeostasis and bone formation, respectively. We aim to investigate the association between the serum(s) and synovial fluid (SF) Dkk-1 and sclerostin levels and disease severity in patients with primary knee OA. Forty patients aged 56-87years with primary knee OA and 20 healthy individuals were recruited. Weight-bearing anteroposterior radiographs of the affected knee were used to determine the disease severity according to Kellgren and Lawrence criteria. Dkk-1 and sclerostin levels in serum and SF were measured by ELISA. SF Dkk-1 levels were significantly higher in the OA, compared to control group (180±182 vs 128±330pg/ml, p<0.001). However, OA patients did not differ significantly regarding the sDkk-1 concentrations compared to healthy controls (1289.8pg/ml vs 1214.1, respectively, p=0.630). SF Dkk-1 levels in Kellgren and Lawrence (KL) grade 4 were significantly elevated compared to those of KL grades 2 and 3 (1.97 vs 2.23pg/ml, p=0.017, log transformed because data were not normally distributed), whereas sDkk-1 levels between those groups demonstrated marginally statistically significant difference (1111.8 vs 1415.9pg/ml, p=0.057). SFSclerostin and sSclerostin levels did not have any significant difference between the OA and control groups. SF Dkk-1 levels are positively related to the severity of joint damage in knee OA. Sclerostin levels failed to substantiate an association to knee OA progression. Dkk-1 could play a potential role in the degenerative process of OA. Thus, DKK-1 may emerge as a promising future therapeutic manipulation of OA.