Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression changes in early disease. In this study, we quantified gene expression changes in the synovium of osteoarthritis-affected joints using an equine metacarpophalangeal joint (MCPJ) chip model of early PTOA. Synovial samples were collected arthroscopically from the MCPJ of 11 adult horses before (preOA) and after (OA) surgical induction of osteoarthritis and from sham-operated joints. After sequencing synovial RNA, Salmon was used to quasi-map reads and quantify transcript abundances. Differential expression analysis with the limma-trend method used a fold-change cutoff of log2(1.1). Functional annotation was performed with PANTHER at FDR < 0.05. Pathway and network analyses were performed in Reactome and STRING, respectively. RNA was sequenced from 28 samples (6 preOA, 11 OA, 11 sham). “Sham” and “preOA” were not different and were grouped. Three hundred ninety-seven genes were upregulated and 365 downregulated in OA synovium compared to unaffected. Gene ontology (GO) terms related to extracellular matrix (ECM) organization, angiogenesis, and cell signaling were overrepresented. There were 17 enriched pathways, involved in ECM turnover, protein metabolism, and growth factor signaling. Network analysis revealed clusters of differentially expressed genes involved in ECM organization, endothelial regulation, and cellular metabolism. Enriched pathways and overrepresented GO terms reflected a state of high metabolic activity and tissue turnover in OA-affected tissue, suggesting that the synovium may retain the capacity to support healing and homeostasis in early disease. Limitations of this study include small sample size and capture of one point post-injury. Differentially expressed genes within key pathways may represent potential diagnostic markers or therapeutic targets for PTOA. Mechanistic validation of these findings is an important next step.

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差异基因表达分析揭示了马模型中创伤后早期骨关节炎的重要途径

创伤后骨关节炎（PTOA）是马匹运动员普遍且重要的问题。它是整个关节的疾病，滑膜由于其在炎症中的作用而被认为是疾病发作和进展的关键因素。开发用于PTOA早期诊断和治疗的有效工具仍然是一个遥不可及的目标。改变的基因表达代表了最早可识别的疾病相关变化，并且可以提供有关疾病发病机理的有价值信息，并确定潜在的治疗靶标。但是，研究早期疾病中全球基因表达变化的工作很少。在这项研究中，我们使用早期PTOA的马掌指关节（MCPJ）芯片模型量化了骨关节炎影响关节滑膜中基因表达的变化。在手术诱导骨关节炎之前（preOA）和手术后（OA）以及假手术关节从11匹成年马的MCPJ关节镜下收集滑膜样品。在对滑膜RNA测序后，将Salmon用于准图读取和定量转录本丰度。使用limma-trend方法进行的差异表达分析使用了log2（1.1）的倍数变化临界值。使用PANTHER以FDR <0.05进行功能注释。通路和网络分析分别在Reactome和STRING中进行。从28个样品（6个preOA，11个OA，11个假样品）中对RNA进行了测序。“假”和“ preOA”没有区别，被分组。与未受影响的相比，OA滑膜中有379个基因被上调，而365个基因被下调。与细胞外基质（ECM）的组织，血管生成，和细胞信号被过度代表。有17条富集的途径，涉及ECM转换，蛋白质代谢和生长因子信号传导。网络分析揭示了与ECM组织，内皮调节和细胞代谢有关的差异表达基因簇。丰富的途径和过度代表的GO术语反映了受OA影响的组织中高代谢活性和组织更新的状态，这表明滑膜可能保留了早期疾病中支持愈合和体内平衡的能力。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。有17条富集的途径，涉及ECM转换，蛋白质代谢和生长因子信号传导。网络分析揭示了与ECM组织，内皮调节和细胞代谢有关的差异表达基因簇。丰富的途径和过度代表的GO术语反映了受OA影响的组织中高代谢活性和组织更新的状态，这表明滑膜可能保留了早期疾病中支持愈合和体内平衡的能力。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。有17条富集的途径，涉及ECM转换，蛋白质代谢和生长因子信号传导。网络分析揭示了与ECM组织，内皮调节和细胞代谢有关的差异表达基因簇。丰富的途径和过度代表的GO术语反映了受OA影响的组织中高代谢活性和组织更新的状态，这表明滑膜可能保留了早期疾病中支持愈合和体内平衡的能力。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。和生长因子信号传导。网络分析揭示了与ECM组织，内皮调节和细胞代谢有关的差异表达基因簇。丰富的途径和过度代表的GO术语反映了受OA影响的组织中高代谢活性和组织更新的状态，这表明滑膜可能保留了早期疾病中支持愈合和体内平衡的能力。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。和生长因子信号传导。网络分析揭示了与ECM组织，内皮调节和细胞代谢有关的差异表达基因簇。丰富的途径和过度代表的GO术语反映了受OA影响的组织中高代谢活性和组织更新的状态，这表明滑膜可能保留了早期疾病中支持愈合和体内平衡的能力。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。和细胞代谢。丰富的途径和过度代表的GO术语反映了受OA影响的组织中高代谢活性和组织更新的状态，这表明滑膜可能保留了早期疾病中支持愈合和体内平衡的能力。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。和细胞代谢。丰富的途径和过度代表的GO术语反映了受OA影响的组织中高代谢活性和组织更新的状态，这表明滑膜可能保留了早期疾病中支持愈合和体内平衡的能力。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。该研究的局限性包括样本量小和损伤后仅捕获一点。关键途径中差异表达的基因可能代表了PTOA的潜在诊断标记或治疗靶标。对这些发现进行机械验证是下一步的重要步骤。