OBJECTIVE This study aimed to assess the association between synovial fluid (SF) metabolites and magnetic resonance imaging (MRI) measurements of cartilage biochemical composition to identify potential SF biomarkers for detecting the early onset of cartilage degeneration in a rabbit model. METHODS Both knees of 12 New Zealand White rabbits were used. The anterior cruciate ligament transection (ACLT) model was performed on right knees, and the sham surgery on left knees. MRI UTE-T2* scanning and SF sample collection were performed on ACLT knees at 4 and 8 weeks postsurgery and on sham surgery knees at 4 weeks postsurgery. Ultra-performance liquid chromatography-mass spectrometry and multivariate statistical analysis were used to distinguish samples in three groups. Pathway and receiver operating characteristic analyses were utilized to identify potential metabolite biomarkers. RESULTS There were 12 knees in sham surgery models, 11 in ACLT models at 4 weeks postsurgery, and 10 in ACLT models at 8 weeks postsurgery. UTE-T2* values for the lateral tibia cartilage showed significant decreases over the study period. Levels of 103 identified metabolites in SF were markedly different among three groups. Furthermore, 24 metabolites were inversely correlated with UTE-T2* values of the lateral tibia cartilage, while hippuric acid was positively correlated with UTE-T2* values of the lateral tibia cartilage. Among 25 potential markers, N1-acetylspermidine, 2-amino-1,3,4-octadecanetriol, l-phenylalanine, 5-hydroxy-l-tryptophan, and l-tryptophan were identified as potential biomarkers with high area under the curve values and Pearson correlation coefficients. CONCLUSION Five differential metabolites in SF were found as potential biomarkers for the early detection of cartilage degeneration in the rabbit ACLT model.

中文翻译：

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兔前交叉韧带横断模型中代谢途径的紊乱和早期软骨退化的潜在生物标志物组的鉴定。

目的 本研究旨在评估滑液 (SF) 代谢物与软骨生化成分的磁共振成像 (MRI) 测量之间的关联，以确定潜在的 SF 生物标志物，以检测兔模型中软骨退化的早期发病。方法使用12只新西兰大白兔的双膝。右膝进行前交叉韧带横断（ACLT）模型，左膝进行假手术。在术后 4 周和 8 周对 ACLT 膝关节进行 MRI UTE-T2* 扫描和 SF 样本采集，并在术后 4 周对假手术膝关节进行。采用超高效液相色谱-质谱法和多元统计分析方法区分三组样品。通路和接受者操作特征分析用于识别潜在的代谢物生物标志物。结果假手术模型12膝，术后4周ACLT模型11膝，术后8周ACLT模型10膝。胫骨外侧软骨的 UTE-T2* 值在研究期间显着下降。SF 中 103 种已鉴定代谢物的水平在三组之间存在显着差异。此外，24 种代谢物与胫骨外侧软骨的 UTE-T2* 值呈负相关，而马尿酸与胫骨外侧软骨的 UTE-T2* 值呈正相关。在 25 种潜在标志物中，N1-乙酰亚精胺、2-氨基-1,3,4-十八烷三醇、l-苯丙氨酸、5-羟基-l-色氨酸、和 l-色氨酸被确定为具有高曲线下面积和 Pearson 相关系数的潜在生物标志物。结论 SF 中的五种差异代谢物被发现可作为早期检测兔 ACLT 模型中软骨退变的潜在生物标志物。