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Serum levels of the bone turnover markers dickkopf-1, osteoprotegerin, and TNF-α in knee osteoarthritis patients

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Abstract

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.

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Acknowledgments

This work was supported by the Projects of International Cooperation and Exchanges NSFC (81420108021), National Key Technology Support Program (2015BAI08B02), Excellent Young Scholars NSFC (81622033), Jiangsu Provincial Key Medical Center Foundation, Jiangsu Provincial Medical Talent Foundation, and Jiangsu Provincial Medical Outstanding Talent Foundation. We thank the patients and their families who donated their blood samples for this study.

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Authors and Affiliations

  1. 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

    Sicong Min, Chao Wang, Wanli Lu, Zhihong Xu, Dongquan Shi, Dongyang Chen, Huajian Teng & Qing Jiang

  2. Laboratory for Bone and Joint Disease, Model Animal Research Center (MARC), Nanjing University, Nanjing, 210093, Jiangsu, People’s Republic of China

    Sicong Min, Chao Wang, Wanli Lu, Zhihong Xu, Dongquan Shi, Dongyang Chen, Huajian Teng & Qing Jiang

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  1. Sicong Min
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Correspondence to Huajian Teng or Qing Jiang.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Min, S., Wang, C., Lu, W. et al. Serum levels of the bone turnover markers dickkopf-1, osteoprotegerin, and TNF-α in knee osteoarthritis patients. Clin Rheumatol 36, 2351–2358 (2017). https://doi.org/10.1007/s10067-017-3690-x

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