Theologis Thomas, Efstathopoulos Nikolaos, Nikolaou Vasileios, Charikopoulos Ioannis, Papapavlos Ioannis, Kokkoris Panayiotis, Papatheodorou Athanasios, Nasiri-Ansari Narjes, Kassi Eva
Department of Trauma and Orthopaedics, Thriasio General Hospital-NHS, G. Gennimata Avenue, 19600, Magoula, Attica, Greece.
2nd Department of Trauma and Orthopedics, National and Kapodistrian University of Athens, 2-4 Agias Olgas Str, 14233, Nea Ionia, Athens, Greece.
Clin Rheumatol. 2017 Aug;36(8):1865-1872. doi: 10.1007/s10067-017-3640-7. Epub 2017 Apr 27.
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 56-87 years 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 ± 330 pg/ml, p < 0.001). However, OA patients did not differ significantly regarding the sDkk-1 concentrations compared to healthy controls (1289.8 pg/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 2.23 pg/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 1415.9 pg/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.
原发性膝关节骨关节炎（OA）会导致中老年人残疾。Dickkopf-1（Dkk-1）和硬化蛋白分别是Wnt/β-连环蛋白信号通路的抑制剂，该信号通路分别参与软骨稳态调节和骨形成。我们旨在研究原发性膝关节OA患者血清和滑液（SF）中Dkk-1和硬化蛋白水平与疾病严重程度之间的关联。招募了40名年龄在56 - 87岁的原发性膝关节OA患者和20名健康个体。根据Kellgren和Lawrence标准，使用患侧膝关节负重前后位X线片来确定疾病严重程度。通过酶联免疫吸附测定法（ELISA）测量血清和SF中的Dkk-1和硬化蛋白水平。与对照组相比，OA组的SF Dkk-1水平显著更高（180±182 vs 128±330 pg/ml，p<0.001）。然而，与健康对照组相比，OA患者的血清Dkk-1浓度没有显著差异（分别为1289.8 pg/ml和1214.1 pg/ml，p = 0.630）。与Kellgren和Lawrence（KL）2级和3级相比，KL 4级的SF Dkk-1水平显著升高（1.97 vs 2.23 pg/ml，p = 0.017，因数据非正态分布进行对数转换），而这些组之间的血清Dkk-1水平显示出边缘统计学显著差异（1111.8 vs 1415.9 pg/ml，p = 0.057）。OA组和对照组之间的SF硬化蛋白和血清硬化蛋白水平没有任何显著差异。SF Dkk-1水平与膝关节OA的关节损伤严重程度呈正相关。硬化蛋白水平未能证实与膝关节OA进展相关。Dkk-1可能在OA的退变过程中发挥潜在作用。因此，DKK-1可能成为未来OA治疗的有前景的手段。
