Relationships between blood leukocyte mitochondrial DNA copy number and inflammatory cytokines in knee osteoarthritis
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Osteoarthritis (OA) is a degenerative articular disorder manifested by cartilage destruction, subchondral sclerosis, osteophytes, and synovitis, resulting in chronic joint pain and physical disability in the elderly. The purpose of this study was to investigate mitochondrial DNA copy number (mtDNACN) and inflammatory cytokines in primary knee OA patients and healthy volunteers. A total of 204 knee OA patients and 169 age-matched healthy volunteers were recruited. Their relative blood leukocyte mtDNACN was assessed by quantitative real-time polymerase chain reaction (qRT-PCR), and ten inflammatory cytokines in their plasma were detected by multiplex immunoassay. Blood leukocyte mtDNACN in the OA group was significantly lower than that in the control group. Leukocyte mtDNACN in the control group was negatively correlated with their age (r=−0.380, P<0.0001), whereas mtDNACN in the OA group was positively correlated with their age (r=0.198, P<0.001). Plasma interleukin-4 (IL-4) and IL-6 were significantly higher in the knee OA group than in the control group. The plasma IL-6 level was positively correlated with blood leukocyte mtDNACN in the OA group (r=0.547, P=0.0014). IL-5 showed as a major factor (coefficient 0.69) in the second dimension of principle components analysis (PCA)-transformed data and was significantly higher in the OA group (P<0.001) as well as negatively correlated with mtDNACN (r=−0.577, P<0.001). These findings suggest that elevation of plasma IL-4 and IL-6 and a relative reduction in mtDNACN might be effective biomarkers for knee OA. IL-5 is a plausible factor responsible for decreasing blood leukocyte mtDNACN in knee OA patients.
Key wordsInflammatory cytokine Blood leukocyte Knee Mitochondrial DNA copy number Osteoarthritis
膝骨关节炎患者全血白细胞线粒体 DNA 复制数量和血浆炎性细胞因子的相关性研究
本实验研究全血白细胞线粒体 DNA 复制数量 (mtDNACN)和血浆炎性细胞因子在膝骨关节炎患者中的变化和其相关性.
探讨了老年 (50~80 岁) 膝骨关节炎患者白细胞 mtDNACN 和血浆炎性细胞因子水平及二者的关系.
分别收集膝骨关节炎组和对照组血液样本并对膝关节评分 (Kellgren-Lawren grading). 使用实时定量聚合酶链反应 (qRT-PCR) 检测相对mtDNACN; 使用多重免疫分析 (multiplex immunoassay) 测定血浆中 10 种炎性细胞因子水平; 应用线性相关、 Logistic 回归和主成分分析 (PCA) 揭示骨关节炎白细胞 mtDNACN 和血浆炎性细胞因子的相关性.
血浆中白介素 4 (IL-4)、 IL-6 和全血白细胞 mtDNACN 可能是膝骨关节炎有效的生物标志物; IL-5 则对 mtDNACN 减少具有潜在的影响.
关键词炎性细胞因子 血液白细胞 膝关节 线粒体 DNA 复制数量 骨关节炎
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Dong ZHAN and Sittisak HONSAWEK conceived and designed the experiments, performed the experimental research, analyzed and interpreted the data, and wrote the manuscript. Aree TANAVALEE, Saran TANTAVISUT, and Srihatach NGARMUKOS collected the samples, and analyzed and interpreted the data. Steven W. EDWARDS contributed reagents, materials, and analysis tools and critically commented on the manuscript. Sittisak HONSAWEK contributed reagents, materials, and analysis tools or data, and finally edited the manuscript. All authors have read and approved the final manuscript. Therefore, all authors have full access to all the data in the study and take responsibility for the integrity and security of the data.
Compliance with ethics guidelines
Dong ZHAN, Aree TANAVALEE, Saran TANTAVISUT, Srihatach NGARMUKOS, Steven W. EDWARDS, and Sittisak HONSAWEK declare that they have no conflict of interest.
The study protocol conformed to the ethical standards outlined in the Declaration of Helsinki of 1975, as revised in 2008 (5) and was approved by the Ethical Committee on Human Research of the Faculty of Medicine, Chulalongkorn University, Thailand. All study subjects were fully informed of the study protocol and procedures prior to participating in the study. Written informed consent was obtained from all participants before any procedures were performed.
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