Acute Molecular Changes in Synovial Fluid Following Human Knee Injury: Association With Early Clinical Outcomes.
Acute Molecular Changes in Synovial Fluid Following Human Knee Injury: Association With Early Clinical Outcomes.
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DOI：
10.1002/art.39677
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发表时间：
2016-09
影响因子：
13.3
通讯作者：
Vincent, Tonia L.
中科院分区：
文献类型：
--
作者：
Watt, Fiona E.;Paterson, Erin;Freidin, Andrew;Kenny, Mark;Judge, Andrew;Saklatvala, Jeremy;Williams, Andy;Vincent, Tonia L.
为了研究在小鼠手术后关节失稳数小时内被发现上调的分子是否也在类似的人类急性膝关节损伤的环境中升高，这种分子反应在个体之间如何变化，以及它是否与患者报告的损伤后3个月的结果有关。对150名近期膝关节结构性损伤患者的血液和滑液(SF)中的7个候选分子进行了分析，这些患者在基线(受伤后8周)以及基线后14天和3个月的血液中。在基线和3个月时进行膝关节损伤和骨关节炎预后评分4(KOOS4)。患者和对照样本使用中尺度发现平台分析或酶联免疫吸附分析进行比较。伤后即刻人SF中有6种分子显著升高：白细胞介素6(IL-6)、单核细胞趋化蛋白1、基质金属蛋白酶3(MMP3)、金属蛋白酶组织抑制因子1(TIMP-1)、激活素A和肿瘤坏死因子刺激基因6(TSG-6)。这与血液测量有低到中等的相关性。6个分子中有3个与基线KOOS4显著相关(SF、IL-6、TIMP-1或TSG-6较高者KOOS4较低)。在调整了其他相关因素后，这3个分子，即基质金属蛋白酶-3和激活素A，都与3个月后KOOS4的改善显著相关。其中，IL-6单独对基线KOOS4和3个月后KOOS4的变化有显著的分子贡献。我们的发现验证了在小鼠模型中确定的组织损伤的相关人类生物标记物。对SF的分析比对血液的分析更准确地反映了这种反应。这种反应与患者在早期报告的结果有关，SF IL-6作为单一的代表性标记物。纵向结果将决定这些分子是否为后续疾病风险的生物标记物。
To investigate whether molecules found to be up‐regulated within hours of surgical joint destabilization in the mouse are also elevated in the analogous human setting of acute knee injury, how this molecular response varies between individuals, and whether it is related to patient‐reported outcomes in the 3 months after injury. Seven candidate molecules were analyzed in blood and synovial fluid (SF) from 150 participants with recent structural knee injury at baseline (<8 weeks from injury) and in blood at 14 days and 3 months following baseline. Knee Injury and Osteoarthritis Outcome Score 4 (KOOS4) was obtained at baseline and 3 months. Patient and control samples were compared using Meso Scale Discovery platform assays or enzyme‐linked immunosorbent assay. Six of the 7 molecules were significantly elevated in human SF immediately after injury: interleukin‐6 (IL‐6), monocyte chemotactic protein 1, matrix metalloproteinase 3 (MMP‐3), tissue inhibitor of metalloproteinases 1 (TIMP‐1), activin A, and tumor necrosis factor–stimulated gene 6 (TSG‐6). There was low‐to‐moderate correlation with blood measurements. Three of the 6 molecules were significantly associated with baseline KOOS4 (those with higher SF IL‐6, TIMP‐1, or TSG‐6 had lower KOOS4). These 3 molecules, MMP‐3, and activin A were all significantly associated with greater improvement in KOOS4 over 3 months, after adjustment for other relevant factors. Of these, IL‐6 alone significantly accounted for the molecular contribution to baseline KOOS4 and change in KOOS4 over 3 months. Our findings validate relevant human biomarkers of tissue injury identified in a mouse model. Analysis of SF rather than blood more accurately reflects this response. The response is associated with patient‐reported outcomes over this early period, with SF IL‐6 acting as a single representative marker. Longitudinal outcomes will determine if these molecules are biomarkers of subsequent disease risk.
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作者：
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