McCaig Institute for Bone and Joint Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
J Orthop Res. 2011 Aug;29(8):1185-92. doi: 10.1002/jor.21404. Epub 2011 Mar 8.
While impossible in humans, the mechanisms of early cartilage, bone and meniscal damage can be quantified after anterior cruciate ligament (ACL) injury in animal models. We utilized an ovine model to determine if the mRNA expression of inflammatory and degradative molecules (IL-1β, IL-6, MMP-1, 2, 3, and 13) in the synovium correlated to changes in joint tissues 2 weeks post-ACL surgery, to test the hypothesis that synovial inflammation is a marker of these changes and possibly their originator. Nine "idealized" ACL autografts were performed and compared with three sham and six normal animals. Using validated protocols, early osteophyte formation, articular cartilage, and meniscal damage were quantified. Synovium was harvested and mRNA expression quantified using qPCR. Multiple linear regression analysis (MLRA) was utilized to correlate synovial mRNA expression in treated and contra-lateral limbs, from all treatment groups with corresponding joint scores. Synovial mRNA expression was significantly elevated in all experimental and sham joints. The MLRA model was a significant predictive tool (p = 0.001, R(2) = 0.70) of gross tissue scores with significant contributions from IL-1β, IL-6, and MMP-3. Findings suggest that this set of synovial biomarkers is predictive (p < 0.009) of early gross changes of joint tissues after arthrotomy and likely directly involved in the relevant mechanisms, particularly early osteophyte formation, in vivo.
虽然在人类中不可能实现,但在前交叉韧带 (ACL) 损伤后,动物模型中可以量化早期软骨、骨和半月板损伤的机制。我们利用绵羊模型来确定滑膜中炎症和降解分子(IL-1β、IL-6、MMP-1、2、3 和 13)的 mRNA 表达是否与 ACL 手术后 2 周关节组织的变化相关,以验证滑膜炎症是这些变化及其可能的起源的标志物的假设。进行了 9 例“理想化”的 ACL 自体移植物,并与 3 例假手术和 6 例正常动物进行了比较。使用经过验证的方案,对早期骨赘形成、关节软骨和半月板损伤进行了量化。采集滑膜并使用 qPCR 定量 mRNA 表达。多元线性回归分析 (MLRA) 用于将治疗组和对侧肢体的滑膜 mRNA 表达与所有治疗组的相应关节评分相关联。所有实验性和假手术关节的滑膜 mRNA 表达均显著升高。MLRA 模型是一种具有统计学意义的预测工具(p=0.001,R²=0.70),可以预测关节组织的大体评分,其中 IL-1β、IL-6 和 MMP-3 有显著贡献。研究结果表明,这组滑膜生物标志物可预测关节切开术后早期关节组织的大体变化(p<0.009),并且可能直接参与相关机制,特别是体内早期骨赘形成。