Abstract

BackgroundOsteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. The aim of this study was to examine plasma and synovial fluid Dkk-1 levels of patients with primary knee OA and to investigate their relationship with disease severity.MethodsThirty-five patients aged 55-83 years with knee OA and 15 healthy individuals were recruited into this study. Disease severity was determined using weight-bearing anteroposterior radiographs of the affected knee. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. Dkk-1 levels in both plasma and synovial fluid were evaluated using enzyme-linked immunosorbent assay.ResultsThe average concentration of circulating Dkk-1 in the knee OA patients was remarkably lower than that of healthy controls (396.0 ± 258.8, 95%CI 307.1-484.9 vs 2348.8 ± 2051.5, 95%CI 1164.3-3533.3 pg/ml, p < 0.0001). Dkk-1 levels in synovial fluid were significantly lower than in paired plasma samples (58.6 ± 31.8, 95%CI 47.7-69.6 vs 396.0 ± 258.8, 95%CI 307.1-484.9 pg/ml, p < 0.001). Furthermore, both plasma and synovial fluid Dkk-1 levels were inversely correlated with radiographic severity (r = -0.78, p < 0.001 and r = -0.42, p = 0.01, respectively). Plasma Dkk-1 levels were also significantly correlated with synovial fluid Dkk-1 levels (r = 0.72, p < 0.001).ConclusionsDkk-1 levels in plasma and synovial fluid are inversely related to the severity of joint damage in knee OA. Dkk-1 could serve as a biochemical marker for determining disease severity and might play a potential role in the pathogenesis of the degenerative process of OA.

Highlights

  • Osteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability

  • Diarra and colleagues have documented that blockade of Dkk-1 reverses the bone-destructive pattern in a mouse model of rheumatoid arthritis to the bone-forming pattern of OA [10], indicating that Dkk-1 is a central regulator of joint remodeling

  • There was no significant difference in body mass index between OA patients and controls (26.6 ± 3.8, 95% confidence intervals (CI) 25.3-28.0 vs 25.5 ± 1.3, 95% confidence intervals (95%CI) 24.6-26.4 kg/m2, p = 0.3)

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Summary

Introduction

Osteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. Osteoarthritis (OA) is the most prevalent joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. It is characterized by the progressive destruction of articular cartilage with joint-space narrowing, osteophyte formation, subchondral sclerosis, and synovitis [1]. Secreted glycoproteins of the Wingless (Wnt) signaling pathway are crucial regulators of cell growth and survival in a variety of human cell types. Dickkopf-1 (Dkk-1) is a secreted protein that has been defined as a direct inhibitor of Wnt/ b-catenin signaling by interacting with the LRP5/6 coreceptors of frizzled [5,6]. Growing evidence has proposed an association between deregulated Wnt signaling components and joint disorders in OA cartilage chondrocyte cultures [13]

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