Department of Molecular Medicine, Scripps Research, La Jolla, CA, 92037, USA; Department of Radiology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Molecular Medicine, Scripps Research, La Jolla, CA, 92037, USA.
Osteoarthritis Cartilage. 2023 Feb;31(2):199-212. doi: 10.1016/j.joca.2022.10.003. Epub 2022 Oct 28.
Transcriptomic changes in joint tissues during the development of osteoarthritis (OA) are of interest for the discovery of biomarkers and mechanisms of disease. The objective of this study was to use the rat medial meniscus transection (MMT) model to discover stage and tissue-specific transcriptomic changes.
Sham or MMT surgeries were performed in mature rats. Cartilage, menisci and synovium were scored for histopathological changes at 2, 4 and 6 weeks post-surgery and processed for RNA-sequencing. Differentially expressed genes (DEG) were used to identify pathways and mechanisms. Published transcriptomic datasets from animal models and human OA were used to confirm and extend present findings.
The total number of DEGs was already high at 2 weeks (723 in meniscus), followed by cartilage (259) and synovium (42) and declined to varying degrees in meniscus and synovium but increased in cartilage at 6 weeks. The most upregulated genes included tenascins. The 'response to mechanical stimulus' and extracellular matrix-related pathways were enriched in both cartilage and meniscus. Pathways that were enriched in synovium at 4 weeks indicate processes related to synovial hyperplasia and fibrosis. Synovium also showed upregulation of IL-11 and several MMPs. The mechanical stimulus pathway included upregulation of the mechanoreceptors PIEZO1, PIEZO2 and TRPV4 and nerve growth factor. Analysis of data from prior RNA-sequencing studies of animal models and human OA support these findings.
These results indicate several shared pathways that are affected during OA in cartilage and meniscus and support the role of mechanotransduction and other pathways in OA pathogenesis.
研究骨关节炎（OA）关节组织的转录组变化对于发现生物标志物和疾病机制具有重要意义。本研究旨在利用大鼠内侧半月板切除术（MMT）模型发现阶段和组织特异性的转录组变化。
对成熟大鼠进行假手术或 MMT 手术。术后 2、4 和 6 周对软骨、半月板和滑膜进行组织病理学评分，并进行 RNA 测序。差异表达基因（DEG）用于识别途径和机制。使用来自动物模型和人类 OA 的已发表转录组数据集来证实和扩展现有发现。
2 周时，DEG 的总数已经很高（半月板中为 723 个），其次是软骨（259 个）和滑膜（42 个），而半月板和滑膜的数量在 6 周时逐渐减少，但软骨的数量增加。上调最明显的基因包括 tenascins。“对机械刺激的反应”和细胞外基质相关途径在软骨和半月板中均有富集。滑膜中在 4 周时富集的途径表明与滑膜增生和纤维化相关的过程。滑膜还上调了 IL-11 和几种 MMPs。机械刺激途径包括机械感受器 PIEZO1、PIEZO2 和 TRPV4 和神经生长因子的上调。对动物模型和人类 OA 的先前 RNA 测序研究数据的分析支持这些发现。
这些结果表明，在软骨和半月板的 OA 过程中存在几个共同受影响的途径，并支持机械转导和其他途径在 OA 发病机制中的作用。
