Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post-traumatic osteoarthritis
Metabolomic serum profiling after ACL injury in rats: A pilot study implicating inflammation and immune dysregulation in post-traumatic osteoarthritis
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DOI：
10.1002/jor.23854
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发表时间：
2018-07-01
影响因子：
2.8
通讯作者：
Baker, Kevin C.
中科院分区：
文献类型：
--
作者：
Maerz, Tristan;Sherman, Eric;Baker, Kevin C.
ACL断裂是创伤后骨关节炎（PTOA）发展的主要风险因素。关于疾病发展的急性全身代谢指标的信息很少。将36只雌性刘易斯大鼠随机分为对照组和非侵袭性前交叉韧带断裂组（ACLR），每组6只。收集血清，并通过H-1核磁共振（NMR）光谱和直接进样与液相色谱（LC）-质谱（MS）/MS（DI-MS）组合进行分析。单变量和多变量统计用于分析代谢组学数据，预测生物标志物模型通过受试者工作特征（ROC）分析进行分析。拓扑路径分析用于确定扰动的途径。通过H-1 NMR和DI-MS鉴定了222种代谢物。ACLR和对照组之间的血清代谢物组差异主要由中链和长链酰基肉毒碱物质组成。此外，发现几种色氨酸代谢物的减少在单变量分析中显着不同，或者对多变量模型分离发挥重要贡献作用。除了酰基肉毒碱和色氨酸代谢物之外，发现甘氨酸、肌肽和D-甘露糖可将ACLR与对照区分开。甘氨酸、9-十六碳烯酰基肉毒碱、反式-2-十二碳烯酰基肉毒碱、亚油酰基肉毒碱、羟基丙酰基肉毒碱和D-甘露糖被鉴定为具有高ROC曲线下面积值和高预测准确度的生物标志物。我们的分析提供了关于炎症过程和免疫失调对ACL损伤后PTOA发生和进展的潜在作用的新信息。由于这些过程通常与炎性关节病有关，因此有必要进行更大规模的研究，阐明它们参与PTOA的发展和进展。(c)2018骨科研究学会。由威利期刊公司出版J Orthop Res 36：1969-1979，2018。
ACL rupture is a major risk factor for post-traumatic osteoarthritis (PTOA) development. Little information exists on acute systemic metabolic indicators of disease development. Thirty-six female Lewis rats were randomized to Control or noninvasive anterior cruciate ligament rupture (ACLR) and to three post-injury time points: 72h, 4 weeks, 10 weeks (n=6). Serum was collected and analyzed by H-1 nuclear magnetic resonance (NMR) spectroscopy and combined direct injection and liquid chromatography (LC)-mass spectrometry (MS)/MS (DI-MS). Univariate and multivariate statistics were used to analyze metabolomic data, and predictive biomarker models were analyzed by receiver operating characteristic (ROC) analysis. Topological pathway analysis was used to identify perturbed pathways. Two hundred twenty-two metabolites were identified by H-1 NMR and DI-MS. Differences in the serum metabolome between ACLR and Control were dominated by medium- and long-chain acylcarnitine species. Further, decreases in several tryptophan metabolites were either found to be significantly different in univariate analysis or to play important contributory roles to multivariate model separation. In addition to acylcarnitines and tryptophan metabolites, glycine, carnosine, and D-mannose were found to differentiate ACLR from Control. Glycine, 9-hexadecenoylcarnitine, trans-2-Dodecenoylcarnitine, linoelaidyl carnitine, hydroxypropionylcarnitine, and D-Mannose were identified as biomarkers with high area under ROC curve values and high predictive accuracies. Our analysis provides new information regarding the potential contribution of inflammatory processes and immune dysregulation to the onset and progression of PTOA following ACL injury. As these processes have most commonly been associated with inflammatory arthropathies, larger-scale studies elucidating their involvement in PTOA development and progression are necessary. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1969-1979, 2018.