Background:

Anterior cruciate ligament (ACL) tears are associated with posttraumatic osteoarthritis, but the early biological changes that initiate joint degeneration after this injury are not well characterized. ACL tears typically result in effusion in the knee, which may provide insight into the initial response of the joint to injuries.

Hypothesis:

Patient- and injury-specific factors are associated with the proteomics of synovial fluid in knees with ACL tears.

Study Design:

Descriptive laboratory study.

Methods:

Synovial fluid was collected from 105 patients (38 male, 67 female) with an acute traumatic ACL tear. Patient- and injury-specific factors such as age, sex, body mass index, time from injury, presence/absence of concomitant meniscal tears, and location of concomitant bone bruises (if present) were recorded. The protein concentration of synovial fluid was measured, followed by benchmarking of samples for multi-affinity high-abundance protein depletion. An isotropically labeled high-resolution nano-liquid chromatography with tandem mass spectrometry–based proteomic approach was used to determine the synovial fluid protein profile. Data were processed, quality controlled, and analyzed computationally for each patient and injury factor.

Results:

The proteomics of synovial fluid from ACL tears was associated with patient sex, injury pattern, and location of bone bruises but not with patient age, body mass index, or time from injury. Knees with an isolated ACL tear had higher glutathione peroxidase 1 (GPX1) and plastin 3 levels than knees with an ACL tear and meniscal tear. A bone bruise on the lateral femoral condyle was associated with elevated leptin and glucose-6-phosphate dehydrogenase (G6PD) levels. A bone bruise on the lateral tibial plateau was associated with decreased GPX1 levels. Male patients had higher matrix metalloproteinase 9 and lower G6PD levels than female patients.

Conclusion:

Patient sex, injury pattern, and bone bruise location were important determinants of the proteomic profile of effusion resulting from ACL tears.

Clinical Relevance:

Longitudinal follow-ups to see if and how proteomic differences relate to clinical outcomes and mechanistic studies to assess the role that specific proteins play in the joint are warranted. Ultimately, these investigations could lead to better approaches to predict clinical outcomes and identify possible interventions to optimize outcomes in these patients.

中文翻译：

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前交叉韧带撕裂患者滑液的蛋白质组学分析

背景：

前交叉韧带 (ACL) 撕裂与创伤后骨关节炎有关，但在此损伤后引发关节退化的早期生物学变化尚未得到很好的表征。ACL 撕裂通常会导致膝关节积液，这可能有助于了解关节对损伤的初始反应。

假设：

患者和损伤特异性因素与 ACL 撕裂膝关节滑液的蛋白质组学有关。

学习规划：

描述性实验室研究。

方法：

从 105 名患有急性外伤性 ACL 撕裂的患者（38 名男性，67 名女性）中收集滑液。记录患者和损伤特定因素，例如年龄、性别、体重指数、受伤时间、是否存在伴随的半月板撕裂以及伴随的骨挫伤（如果存在）的位置。测量滑液中的蛋白质浓度，然后对样品进行基准测试以进行多亲和力高丰度蛋白质消耗。使用基于串联质谱的蛋白质组学方法的各向同性标记的高分辨率纳米液相色谱法来确定滑液蛋白质谱。对每个患者和伤害因素的数据进行处理、质量控制和计算分析。

结果：

ACL 撕裂关节液的蛋白质组学与患者性别、损伤模式和骨挫伤位置相关，但与患者年龄、体重指数或受伤时间无关。孤立的 ACL 撕裂的膝盖比 ACL 撕裂和半月板撕裂的膝盖具有更高的谷胱甘肽过氧化物酶 1 (GPX1) 和 plastin 3 水平。股骨外侧髁上的骨挫伤与瘦素和葡萄糖-6-磷酸脱氢酶 (G6PD) 水平升高有关。外侧胫骨平台的骨挫伤与 GPX1 水平降低有关。与女性患者相比，男性患者的基质金属蛋白酶 9 更高，G6PD 水平更低。

结论：

患者性别、损伤模式和骨挫伤位置是 ACL 撕裂导致的渗出液的蛋白质组学特征的重要决定因素。

临床相关性：

纵向随访以了解蛋白质组学差异是否以及如何与临床结果和机制研究相关，以评估特定蛋白质在关节中的作用是必要的。最终，这些调查可能会导致更好的方法来预测临床结果并确定可能的干预措施以优化这些患者的结果。