Inflammation and Remodelling, Pfizer, Cambridge, MA, USA.
Osteoarthritis Cartilage. 2013 Feb;21(2):339-45. doi: 10.1016/j.joca.2012.10.016. Epub 2012 Nov 7.
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.
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.
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.
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.
我们之前已经证明了 tenascin-C(TN-C)在体外诱导人关节软骨中炎症介质和基质降解的能力。本研究的目的是在急性关节损伤或关节疾病后,观察 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。
本研究共纳入了 164 例膝关节滑液样本,这些样本来自一个横截面便利性队列。诊断组包括膝关节健康对照组、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)。采用酶联免疫吸附试验(ELISA)法检测滑液样本中的 TN-C,并将结果与其他软骨标志物进行相关性分析。同时还监测了接受膝关节不稳定手术的犬膝关节中 TN-C 的释放情况。
与健康对照组相比,所有人类疾病组和接受膝关节不稳定手术的犬膝关节滑液中的 TN-C 水平均显著升高。在人类患者的滑液中,TN-C 水平与 aggrecanase 依赖性 Ala-Arg-Gly-aggrecan(ARG-aggrecan)片段和基质金属蛋白酶 1 和 3 的水平之间存在显著相关性。
我们发现,在人类膝关节受伤、AIA 或 OA 后,TN-C 水平显著升高,且与软骨降解和炎症标志物相关。滑液中的 TN-C 可能具有双重作用,既是关节损伤的标志物,也是进一步关节降解的刺激物。