Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation

Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation
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DOI:
10.1016/j.joca.2012.10.016
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发表时间:
2013-02-01
影响因子:
7
通讯作者:
Lohmander, L. S.
Lohmander, L. S.
中科院分区:
医学2区
文献类型:
--
作者:
Chockalingam, P. S.;Glasson, S. S.;Lohmander, L. S.

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目的:我们先前已证明腱糖蛋白-C(TN - C)在体外人关节软骨中诱导炎症介质和基质降解的能力。本研究的目的是追踪急性关节损伤后或关节疾病中TN - C释放到膝关节滑液中的情况,并将TN - C水平与软骨基质降解和炎症的标志物相关联。 方法:人膝关节滑液样本(n = 164)来自一个横断面便利队列。诊断分组为膝关节健康对照、膝关节前交叉韧带断裂(伴或不伴半月板损伤)、单纯膝关节半月板损伤、急性炎症性关节炎(AIA)和膝关节骨关节炎(OA)。使用酶联免疫吸附测定(ELISA)测量滑液样本中的TN - C,并将结果与其他软骨标志物相关联。还对接受膝关节不稳定手术的犬的关节中TN - C的释放进行了监测。 结果:在所有人类疾病组的关节液以及接受膝关节不稳定手术的犬中,观察到TN - C水平与参照对象相比具有统计学显著升高。在人类患者滑液中的TN - C水平与聚集蛋白聚糖酶依赖性丙氨酸 - 精氨酸 - 甘氨酸 - 聚集蛋白聚糖(ARG - 聚集蛋白聚糖)片段以及基质金属蛋白酶1和3的水平之间观察到具有统计学意义的相关性。 结论:我们发现人膝关节在受伤、AIA或OA后TN - C水平显著升高,且与软骨降解和炎症的标志物相关。滑液中的TN - C可能具有双重作用,既是关节损伤的标志物,又是进一步关节降解的刺激物。(C)2012国际骨关节炎研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: We have previously shown the capacity of tenascin-C (TN-C) to induce inflammatory mediators and matrix degradation in vitro in human articular cartilage. The objective of the present study was to follow TN-C release into knee synovial fluid after acute joint injury or in joint disease, and to correlate TN-C levels with markers of cartilage matrix degradation and inflammation.Method: Human knee synovial fluid samples (n = 164) were from a cross-sectional convenience cohort. Diagnostic groups were knee healthy reference, knee anterior cruciate ligament rupture, with or without concomitant meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples using an enzyme-linked immunosorbent assay (ELISA) and results correlated to other cartilage markers. TN-C release was also monitored in joints of dogs that underwent knee instability surgery.Results: Statistically significantly higher levels of TN-C compared to reference subjects were observed in the joint fluid of all human disease groups and in the dogs that underwent knee instability surgery. Statistically significant correlations were observed between the TN-C levels in the synovial fluid of the human patients and the levels of aggrecanase-dependent Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments and matrix metalloproteinases 1 and 3.Conclusions: We find highly elevated levels of TN-C in human knee joints after injury, AIA or OA that correlated with markers of cartilage degradation and inflammation. TN-C in synovial fluid may serve dual roles as a marker of joint damage and a stimulant of further joint degradation. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.