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Abstract：
Osteoarthritis (OA) is a worldwide joint disease. However, the precise mechanism causing OA remains unclear. Our primary aim was to identify vital biomarkers associated with the mechano-inflammatory aspect of OA, providing potential diagnostic and therapeutic targets for OA. Thirty OA patients who underwent total knee arthroplasty were recruited, and cartilage samples were obtained from both the lateral tibial plateau (LTP) and medial tibial plateau (MTP). GO and KEGG enrichment analyses were performed, and the protein-protein interaction (PPI) assessment was conducted for hub genes. The effect of PSD95 inhibition on cartilage degeneration was also conducted and analyzed. A total of 1247 upregulated and 244 downregulated DEGs were identified. Significant differences were observed between MTP and LTP in mechanical stress-related genes and activated sensory neurons based on a self-contrast model of human knee OA. Cluster analysis identified DLG4 as the hub gene. Cyclic loading stress increased PSD95 (encoded by DLG4) expression in LTP cartilage, and PSD95 inhibitors could alleviate OA progression. This study suggests that inhibiting PSD95 could be a potential therapeutic strategy for preventing articular cartilage degradation.
摘要：
骨关节炎(OA)是一种世界性的关节疾病。然而,导致OA的确切机制尚不清楚.我们的主要目的是确定与OA的机械炎症方面相关的重要生物标志物，为OA提供潜在的诊断和治疗靶点。招募了30例接受全膝关节置换术的OA患者，从胫骨外侧平台（LTP）和胫骨内侧平台（MTP）获得软骨样品。进行了GO和KEGG富集分析，并对hub基因进行蛋白质-蛋白质相互作用（PPI）评估。还进行并分析了PSD95抑制对软骨退变的影响。鉴定了总共1247个上调的DEG和244个下调的DEG。基于人类膝关节OA的自我对比模型，在机械应力相关基因和激活的感觉神经元中，MTP和LTP之间观察到显着差异。聚类分析将DLG4鉴定为hub基因。循环负荷应力增加了LTP软骨中PSD95（由DLG4编码）的表达，PSD95抑制剂可以缓解OA的进展。这项研究表明，抑制PSD95可能是预防关节软骨退化的潜在治疗策略。
