背景:色氨酸2,3-双加氧酶(TDO2)是将色氨酸分解代谢为犬尿氨酸的主要酶。大量研究表明,TDO2与炎症相关疾病有关。然而,其在骨关节炎(OA)中的作用尚未被研究。本研究的目的是探讨OA患者滑膜和滑液(SF)中TDO2的水平及其与临床表现和促炎细胞因子水平的相关性。方法:收集OA患者和手术期间关节外伤患者(对照组)的滑膜和SF样本。采用酶联免疫吸附试验(ELISA)测定TDO2、白细胞介素-1β(IL-1β)、滑膜和SF中的肿瘤坏死因子-α(TNF-α)水平。使用受试者工作特征(ROC)曲线分析评估TDO2在滑膜中区分对照组和OA患者的诊断性能。TDO2水平之间的相关性,OA临床特征,采用Pearson相关分析对促炎细胞因子进行评价。还检查了IL-1β或TNF-α刺激对OA成纤维细胞样滑膜细胞(OA-FLS)中TDO2表达的影响。
结果:TDO2,IL-1β,发现OA患者滑膜中的TNF-α明显高于对照组。ROC曲线分析显示滑膜中TOD2的曲线下面积(AUC)为0.800,敏感性为64.3%,特异性为85.0%,这使得能够区分OA患者与对照组。此外,与正常滑膜成纤维细胞(NSF)相比,OA-FLS中TDO2的蛋白表达上调。此外,滑膜和SF中TDO2水平与IL-1β和TNF-α水平呈显著正相关。滑膜中的TDO2水平也与Kellgren-Lawrence评分呈正相关。此外,IL-1β-或TNF-α-OA-FLS刺激的TDO2蛋白表达明显高于对照FLS。
结论:这些数据表明滑膜中的高TDO2水平可能与促炎细胞因子和OA的严重程度相关。
BACKGROUND: Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme that catabolizes tryptophan to kynurenine. Numerous studies have suggested that TDO2 is involved in inflammation-related diseases. However, its role in osteoarthritis (OA) has not yet been investigated. The aim of the present study was to explore the levels of TDO2 in the synovium and synovial fluid (SF) of patients with OA and its correlation with clinical manifestations and levels of pro-inflammatory cytokines. METHODS : Synovium and SF samples were collected from patients with OA and patients with joint trauma (controls) during surgery. An enzyme-linked immunosorbent assay (ELISA) was used to measure TDO2, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Diagnostic performance of TDO2 in the synovium to discriminate between controls and OA patients was assessed using receiver operating characteristic (ROC) curve analysis. Correlations between TDO2 levels, OA clinical features, and pro-inflammatory cytokines were evaluated using Pearson correlation analysis. Effects of IL-1β or TNF-α stimulation on TDO2 expression in OA-fibroblast-like synoviocytes (OA-FLS) were also examined.
RESULTS: The levels of TDO2, IL-1β, and TNF-α in the synovium of patients with OA were found to be significantly higher than those in controls. ROC curve analysis revealed an area under the curve (AUC) of 0.800 with 64.3% sensitivity and 85.0% specificity of TOD2 in the synovium, which enabled discriminating patients with OA from controls. Moreover, protein expression of TDO2 was upregulated to a greater extent in OA-FLS than in normal synovial fibroblasts (NSF). Furthermore, the levels of TDO2 showed significantly positive correlation with IL-1β and TNF-α levels in the synovium and SF. TDO2 levels in the synovium were also positively correlated with the Kellgren-Lawrence score. Additionally, TDO2 protein expression was significantly increased in IL-1β‒ or TNF-α‒stimulated OA-FLS than in control FLS.
CONCLUSIONS: These data indicate that highTDO2 levels in the synovium can be correlated with pro-inflammatory cytokines and severity of OA.