Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital, School of Medicine, Nanjing University, 321 Zhongshan Road, Nanjing, 210008, Jiangsu, People's Republic of China.
Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing, 210093, Jiangsu, People's Republic of China.
Clin Rheumatol. 2017 Oct;36(10):2351-2358. doi: 10.1007/s10067-017-3690-x. Epub 2017 Jul 4.
Knee osteoarthritis (KOA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Several inflammatory markers and cartilage degradation products can be used as biomarkers in OA. The key factors of bone metabolism in normal joint bone, dickkopf-1 (DKK1) and osteoprotegerin (OPG), interact with Wnt signaling pathway, balancing between bone absorption and bone reconstruction. TNF-α is a key inducer of DKK-1, which belongs to the family of proteins involved in joint remodeling. The present study compared the serum levels of DKK1, TNF-α, and OPG in patients with KOA and healthy controls to analyze the interrelationship and the severity of joint destruction. One hundred forty-eight patients with KOA and 101 healthy controls were enrolled in this study. Anteroposterior knee radiographs determined the severity of the disease in the affected knee. The radiographic grading of KOA was performed by the Kellgren-Lawrence criteria. Serum levels of DKK-1, TNF-α, and OPG were estimated using the multiplex particle-based flow cytometry. Higher serum levels of OPG and TNF-α were observed in KOA than the controls; KOA patients showed a lower serum level of DKK-1, whereas the serum levels of DKK1 correlated with the progression of KOA. The serum levels of TNF-α, OPG, and DKK-1 correlated with incident KOA. In the ROC curve analysis, DKK1 levels showed 78.6% sensitivity and 40% specificity, TNF-α levels showed 74.1% sensitivity and 76.0% specificity, and OPG showed 88.1% sensitivity and 81% specificity in predicting severe KOA. In the univariate and multivariate analyses, TNF-α and OPG emerged as independent predictors of severe KOA. This study, for the first time, combined TNF-α, DKK1, and OPG as valuable biological markers in predicting the severity of KOA radiographically in the clinic. This study also supported the inflammation-induced DKK1 and OPG in OA pathogenesis.
膝骨关节炎（KOA）是一种常见的退行性关节疾病，可引起疼痛、僵硬、运动受限、肿胀、弹响和残疾。几种炎症标志物和软骨降解产物可作为 OA 的生物标志物。正常关节骨中的骨代谢关键因素，Dickkopf-1（DKK1）和骨保护素（OPG），与 Wnt 信号通路相互作用，在骨吸收和骨重建之间保持平衡。TNF-α 是 DKK-1 的关键诱导因子，属于参与关节重塑的蛋白质家族。本研究比较了 KOA 患者和健康对照组的血清 DKK1、TNF-α 和 OPG 水平，以分析关节破坏的严重程度。本研究纳入了 148 例 KOA 患者和 101 例健康对照者。膝关节前后位 X 线片确定了受影响膝关节的疾病严重程度。采用 Kellgren-Lawrence 标准对 KOA 的 X 线分级进行评估。采用基于颗粒的多重流式细胞术估计 DKK1、TNF-α 和 OPG 的血清水平。与对照组相比，KOA 患者的 OPG 和 TNF-α 血清水平较高；KOA 患者的 DKK1 血清水平较低，而 DKK1 血清水平与 KOA 的进展相关。TNF-α、OPG 和 DKK1 的血清水平与新发 KOA 相关。在 ROC 曲线分析中，DKK1 水平的灵敏度为 78.6%，特异性为 40%，TNF-α 水平的灵敏度为 74.1%，特异性为 76.0%，OPG 水平的灵敏度为 88.1%，特异性为 81%，在预测严重 KOA 方面具有较高的预测价值。在单因素和多因素分析中，TNF-α 和 OPG 是严重 KOA 的独立预测因子。本研究首次将 TNF-α、DKK1 和 OPG 联合作为预测 KOA 严重程度的有价值的生物标志物。本研究还支持 OA 发病机制中的炎症诱导的 DKK1 和 OPG。
