Post-Traumatic Osteoarthritis in Mice Following Mechanical Injury to the Synovial Joint.
Post-Traumatic Osteoarthritis in Mice Following Mechanical Injury to the Synovial Joint.
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DOI：
10.1038/srep45223
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发表时间：
2017-03-27
影响因子：
4.6
通讯作者：
Sandell LJ
中科院分区：
文献类型：
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作者：
Rai MF;Duan X;Quirk JD;Holguin N;Schmidt EJ;Chinzei N;Silva MJ;Sandell LJ
我们研究了机械损伤引起的膝关节创伤后骨关节炎（PTOA）的病变特征谱。我们假设，小鼠膝关节稳定性的改变再现了PTOA的分子和结构特征，这将提示人类潜在的治疗靶点。来自两个重组近交系（LGXSM-6和LGXSM-33）的八周龄雄性小鼠的右膝经受轴向胫骨压缩。施加了三个单独的载荷大小：6 N、9 N和12 N。左膝关节作为非负荷对照。小鼠在负荷后5、9、14、28和56天处死，通过组织学、免疫染色、显微CT和磁共振成像评估整个膝关节的变化。我们观察到，胫骨压缩破坏关节稳定性的前交叉韧带断裂（除了6 N），并引发了一系列的时间和地形特征的PTOA。这些特征包括软骨细胞外基质损失而无蛋白聚糖替代、第5天软骨细胞凋亡、第14天出现滑膜炎、骨赘、异位钙化和半月板病理。这些发现为人类关节损伤如何导致PTOA提供了一个合理的模型和全关节方法。软骨细胞凋亡、滑膜炎和异位钙化似乎是潜在治疗干预的目标。
We investigated the spectrum of lesions characteristic of post-traumatic osteoarthritis (PTOA) across the knee joint in response to mechanical injury. We hypothesized that alteration in knee joint stability in mice reproduces molecular and structural features of PTOA that would suggest potential therapeutic targets in humans. The right knees of eight-week old male mice from two recombinant inbred lines (LGXSM-6 and LGXSM-33) were subjected to axial tibial compression. Three separate loading magnitudes were applied: 6N, 9N, and 12N. Left knees served as non-loaded controls. Mice were sacrificed at 5, 9, 14, 28, and 56 days post-loading and whole knee joint changes were assessed by histology, immunostaining, micro-CT, and magnetic resonance imaging. We observed that tibial compression disrupted joint stability by rupturing the anterior cruciate ligament (except for 6N) and instigated a cascade of temporal and topographical features of PTOA. These features included cartilage extracellular matrix loss without proteoglycan replacement, chondrocyte apoptosis at day 5, synovitis present at day 14, osteophytes, ectopic calcification, and meniscus pathology. These findings provide a plausible model and a whole-joint approach for how joint injury in humans leads to PTOA. Chondrocyte apoptosis, synovitis, and ectopic calcification appear to be targets for potential therapeutic intervention.