Knee osteoarthritis (KOA) is characterized by mitochondrial damage and increased inflammation. Circulating cell-free mitochondrial DNA (ccf-mtDNA), which originates from damaged mitochondria, is an endogenous damage-associated molecular pattern (DAMPs) molecule that may trigger inflammation and is recognized as a potential biomarker for various diseases. In this study, we investigated the potential association between plasma ccf-mtDNA content and its use as a diagnostic biomarker in patients with KOA. We collected plasma samples from patients with KOA and healthy controls (HC). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect ccf-mtDNA content in the plasma samples. We used the Kellgren–Lawrence (K-L) classification criteria to classify patients with KOA into four grades: I-IV. Disease severity in patients with KOA was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Next, Spearman analysis was performed to observe the correlation between ccf-mtDNA content and the K-L classification and WOMAC score. Logistic regression analysis was used to evaluate the relationship between ccf-mtDNA and KOA risk. In total, we enrolled 60 patients with KOA and HC who were matched for age, sex, and body mass index (BMI). We found that plasma ccf-mtDNA contents were significantly higher in patients with KOA (median, 2.44; quartile range, 1.10–3.79) than in HC (median, 1.08; quartile range, 0.52–2.12) (P < 0.0001). Plasma ccf-mtDNA content sequentially increased following the KOA class I-IV group (P = 0.040) and positively correlated with the K-L classification (r = 0.369, P = 0.004) and WOMAC scores (r = 0.343, P = 0.007). The ccf-mtDNA content did not significantly differ between patients with bilateral and those with single KOA (P = 0.083). Patients with high levels of ccf-mtDNA had a significantly increased risk of KOA compared with those with low levels of ccf-mtDNA (odds ratio [OR], 4.15, 95% confidence interval [CI], 1.71–10.07; P = 0.002). Quartile analysis revealed a significant dose-dependent association (P trend < 0.001). Our study’s findings showed that plasma ccf-mtDNA was highly expressed in patients with KOA compared with HC. Furthermore, ccf-mtDNA content is significantly associated with the severity and risk of KOA. Therefore, its detection may provide insight into the prevention and treatment of KOA.

中文翻译：

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膝骨关节炎患者循环游离线粒体 DNA 含量与膝关节变性严重程度的相关性：一项横断面研究


膝骨关节炎 （KOA） 的特征是线粒体损伤和炎症增加。循环游离线粒体 DNA （ccf-mtDNA） 来源于受损的线粒体，是一种内源性损伤相关分子模式 （DAMPs） 分子，可能引发炎症，被认为是各种疾病的潜在生物标志物。在这项研究中，我们调查了血浆 ccf-mtDNA 含量与其作为 KOA 患者诊断生物标志物之间的潜在关联。我们收集了 KOA 患者和健康对照 （HC） 患者的血浆样本。随后，采用实时定量聚合酶链反应 （qRT-PCR） 检测血浆样本中 ccf-mtDNA 含量。我们使用 Kellgren-Lawrence （K-L） 分类标准将 KOA 患者分为四个等级： I-IV。使用西安大略大学和麦克马斯特大学骨关节炎指数 （WOMAC） 评估 KOA 患者的疾病严重程度。接下来，进行 Spearman 分析以观察 ccf-mtDNA 含量与 K-L 分类和 WOMAC 评分之间的相关性。采用 Logistic 回归分析评价 ccf-mtDNA 与 KOA 风险之间的关系。我们总共招募了 60 例 KOA 和 HC 患者，他们的年龄、性别和体重指数 （BMI） 相匹配。我们发现 KOA 患者血浆 ccf-mtDNA 含量 （中位数，2.44;四分位数范围，1.10-3.79） 显著高于 HC 患者 （中位数，1.08;四分位数范围，0.52-2.12） （P < 0.0001）。血浆 ccf-mtDNA 含量在 KOA I-IV 类组 （P = 0.040） 之后依次增加，并与 K-L 分类 （r = 0.369，P = 0.004） 和 WOMAC 评分 （r = 0.343，P = 0.007） 呈正相关。 双侧 KOA 患者和单侧 KOA 患者 ccf-mtDNA 含量无显著差异 （P = 0.083）。与 ccf-mtDNA 水平低的患者相比，高水平 ccf-mtDNA 患者发生 KOA 的风险显著增加（比值比 [OR]，4.15,95% 置信区间 [CI]，1.71-10.07;P = 0.002）。四分位数分析显示显著的剂量依赖性关联 （P 趋势 < 0.001）。我们的研究结果表明，与 HC 相比，血浆 ccf-mtDNA 在 KOA 患者中高表达。此外，ccf-mtDNA 含量与 KOA 的严重程度和风险显著相关。因此，其检测可能为 KOA 的预防和治疗提供见解。