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Identification of novel biomarkers for arthrofibrosis after total knee arthroplasty in animal models and clinical patients

机译：鉴定动物模型和临床患者总膝关节置换术后关节纤维化的新生物标志物

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Background Arthrofibrosis is a debilitating complication after total knee arthroplasty (TKA) which becomes a considerable burden for both patients and clinical practitioners. Our study aimed to identify novel biomarkers and therapeutic targets for drug discovery. Methods Potential biomarker genes were identified based on bioinformatic analysis. Twelve male New Zealand white rabbits underwent surgical fixation of unilateral knees to mimics the joint immobilization of the clinical scenario after TKA surgery. Macroscopic assessment, hydroxyproline content determination, and histological analysis of tissue were performed separately after 3-days, 1-week, 2-weeks, and 4-weeks of fixation. We also enrolled 46 arthrofibrosis patients and 92 controls to test the biomarkers. Clinical information such as sex, age, range of motion (ROM), and visual analogue scale (VAS) was collected by experienced surgeons Findings Base on bioinformatic analysis, transforming growth factor-beta receptor 1 (TGFBR1) was identified as the potential biomarkers. The level of TGFBR1 was significantly raised in the rabbit synovial tissue after 4-weeks of fixation ( p 0.05). TGFBR1 also displayed a highly positive correlation with ROM loss and hydroxyproline contents in the animal model. TGFBR1 showed a significantly higher expression level in arthrofibrosis patients with a receiver operating characteristic (ROC) area under curve (AUC) of 0.838. TGFBR1 also performed positive correlations with VAS baseline (0.83) and VAS after 1 year (0.76) while negatively correlated with ROM baseline (-0.76) in clinical patients. Interpretation Our findings provided novel biomarkers for arthrofibrosis diagnosis and uncovered the role of TGFBR1. This may contribute to arthrofibrosis prevention and therapeutic drug discovery.
机译：背景技术关节纤维化是膝关节间关节膜成形术（TKA）后的衰弱并发症，这对于患者和临床从业者来说是具有相当大的负担。我们的研究旨在识别药物发现的新型生物标志物和治疗目标。方法基于生物信息分析鉴定潜在的生物标志物基因。十二只男性新西兰白兔经过手术固定单侧膝盖以模仿TKA手术后临床情景的联合固定。在3天，1周，2周和固定4周后单独进行宏观评估，羟脯氨酸含量测定和组织的组织学分析。我们还注册了46例患有46例患者和92例对照来测试生物标志物。经验丰富的外科医生在生物信息分析中，通过经验丰富的外科医生发现，临床信息如性别，年龄，运动范围（ROM）和视觉模拟量表（VAS），将生长因子-βα受体1（TGFBR1）鉴定为潜在的生物标志物。在固定4周后，在兔滑膜组织中，TGFBR1的水平显着升高（P <0.05）。 TGFBR1还展示了动物模型中的ROM损失和羟脯氨酸含量的高度正相关。 TGFBR1在曲线（AUC）的接收器操作特征（ROC）面积为0.838的曲线上显示出显着更高的表达水平。 TGFBR1还与VAS基线（0.83）和VAS进行正相关性，而1年后（0.76），同时在临床患者中与ROM基线（-0.76）负相关。解释我们的调查结果为关节纤维化诊断提供了新的生物标志物，并发现了TGFBR1的作用。这可能有助于节肢动物预防和治疗药物发现。

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