Intema Femke, DeGroot Jeroen, Elshof Bram, Vianen Marieke E, Yocum Sue, Zuurmond Annemarie, Mastbergen Simon C, Lafeber Floris P
Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, F.02.127, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
J Orthop Res. 2008 Nov;26(11):1471-7. doi: 10.1002/jor.20681.
In studies aimed at local treatment of experimental osteoarthritis (OA) it is optimal to have an internal (untreated) OA control. Such an approach excludes interanimal variation, and allows paired statistical evaluation of treatment efficacy. For this purpose, we developed and characterized a bilateral version of the canine Groove model. We hypothesized that the bilateral version of the canine Groove model would show consistent and clear development of features of OA similar to those found in the unilateral version. In six Beagle dogs, grooves were surgically made in the articular cartilage of the femoral condyles of both knee joints. Six additional dogs underwent bilateral sham surgery. The degree of OA was quantified 20 weeks after surgery and was compared in retrospect to 23 animals that undergone the same procedure in a single knee joint with the contralateral knee serving as a non-OA control. Bilateral groove surgery resulted in OA. This was based on the observed ineffective repair response in which an increase in proteoglycan synthesis, a diminished retention of these newly formed proteoglycans, and an enhanced loss of resident proteoglycans resulted in a decreased cartilage proteoglycan content. These biochemical effects were corroborated by clear histological features of OA. All these effects were found in femor as well as in the (surgically untouched) tibia. Interestingly, features of OA were slightly more severe in the bilateral model than in the unilateral variant. The bilateral canine Groove model showed consistent and clear development of features of OA, comparable to the unilateral model.
在旨在对实验性骨关节炎（OA）进行局部治疗的研究中，设置内部（未治疗）OA对照是最佳选择。这种方法排除了动物个体间的差异，并允许对治疗效果进行配对统计评估。为此，我们开发并描述了犬类凹槽模型的双侧版本。我们假设犬类凹槽模型的双侧版本将显示出与单侧版本相似的OA特征的一致且明显的发展。在6只比格犬中，通过手术在两个膝关节股骨髁的关节软骨上制造凹槽。另外6只犬接受双侧假手术。术后20周对OA程度进行量化，并回顾性地与23只在单个膝关节进行相同手术且对侧膝关节作为非OA对照的动物进行比较。双侧凹槽手术导致了OA。这是基于观察到的无效修复反应，即蛋白聚糖合成增加、这些新形成的蛋白聚糖保留减少以及驻留蛋白聚糖损失增加导致软骨蛋白聚糖含量降低。这些生化效应得到了OA明显组织学特征的证实。所有这些效应在股骨以及（未手术处理的）胫骨中均有发现。有趣的是，双侧模型中的OA特征比单侧变体略为严重。双侧犬类凹槽模型显示出与单侧模型相当的OA特征的一致且明显的发展。
