Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, United States; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, United States.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, United States.
Osteoarthritis Cartilage. 2019 Feb;27(2):294-303. doi: 10.1016/j.joca.2018.10.007. Epub 2018 Nov 16.
To characterize local disease progression of the medial meniscus transection (MMT) model of post-traumatic osteoarthritis (OA) at the molecular level, in order to establish a baseline for therapeutic testing at the preclinical stage.
Weight-matched male Lewis rats underwent MMT or sham surgery on the left limb with the right leg as contralateral control. At 1 and 3 weeks post-surgery, tissues were harvested from different areas of the articular cartilage (medial and lateral tibial plateaus, and medial osteophyte region) and synovium (medial and lateral), and analyzed separately. RNA was extracted and used for microarray (RT-PCR) analysis.
Gene expression changes due to surgery were isolated to the medial side of the joint. Gene changes in chondrocyte phenotype of the medial tibial plateau cartilage preceded changes in tissue composition genes. Differences in inflammatory markers were only observed at the osteophyte region at 3 weeks post-surgery. There was surgical noise in the synovium at week 1, which dissipated at week 3. At this later timepoint, meniscal instability resulted in elevated expression of matrix degradation proteins and osteogenic markers in the synovium and cartilage.
These results suggest feedback interactions between joint tissues during disease progression. Regional tissue expression differences found in MMT joints indicated similar pathophysiology to human OA, and provided novel insights about this degeneration model. The examination of gene expression at a localized level in multiple tissues provides a well-characterized baseline to evaluate mechanistic effects of potential therapeutic agents on OA disease progression in the MMT model.
从分子水平上描述创伤后骨关节炎（OA）内侧半月板横断（MMT）模型的局部疾病进展，以便为临床前阶段的治疗试验建立基线。
体重匹配的雄性 Lewis 大鼠在左侧肢体进行 MMT 或假手术，右侧肢体作为对侧对照。在手术后 1 周和 3 周，从关节软骨（内侧和外侧胫骨平台，以及内侧骨赘区域）和滑膜（内侧和外侧）的不同区域采集组织，并分别进行分析。提取 RNA 并用于微阵列（RT-PCR）分析。
手术引起的基因表达变化仅限于关节内侧。内侧胫骨平台软骨软骨细胞表型的基因变化先于组织组成基因的变化。只有在术后 3 周时才观察到骨赘区域的炎症标志物差异。滑膜在第 1 周存在手术噪声，在第 3 周消失。在稍后的时间点，半月板不稳定导致滑膜和软骨中基质降解蛋白和成骨标志物的表达升高。
这些结果表明在疾病进展过程中关节组织之间存在反馈相互作用。MMT 关节中发现的局部组织表达差异表明与人类 OA 具有相似的病理生理学，并为该退变模型提供了新的见解。在多个组织中进行局部基因表达的检查为评估潜在治疗剂对 MMT 模型中 OA 疾病进展的机制影响提供了一个特征良好的基线。
