The Second Affiliated Hospital of Harbin Medical University, Department of Orthopedics Surgery, Harbin Medical University, Harbin, China.
Department of Orthopedics, Harbin First Hospital, Harbin, China.
PeerJ. 2024 May 28;12:e17417. doi: 10.7717/peerj.17417. eCollection 2024.
Osteoarthritis (OA) is a degenerative disease requiring additional research. This study compared gene expression and immune infiltration between lesioned and preserved subchondral bone. The results were validated using multiple tissue datasets and experiments.
Differentially expressed genes (DEGs) between the lesioned and preserved tibial plateaus of OA patients were identified in the GSE51588 dataset. Moreover, functional annotation and protein-protein interaction (PPI) network analyses were performed on the lesioned and preserved sides to explore potential therapeutic targets in OA subchondral bones. In addition, multiple tissues were used to screen coexpressed genes, and the expression levels of identified candidate DEGs in OA were measured by quantitative real-time polymerase chain reaction. Finally, an immune infiltration analysis was conducted.
A total of 1,010 DEGs were identified, 423 upregulated and 587 downregulated. The biological process (BP) terms enriched in the upregulated genes included "skeletal system development", "sister chromatid cohesion", and "ossification". Pathways were enriched in "Wnt signaling pathway" and "proteoglycans in cancer". The BP terms enriched in the downregulated genes included "inflammatory response", "xenobiotic metabolic process", and "positive regulation of inflammatory response". The enriched pathways included "neuroactive ligand-receptor interaction" and "AMP-activated protein kinase signaling". JUN, tumor necrosis factor , and interleukin-1 were the hub genes in the PPI network. Collagen XI A1 and leucine-rich repeat-containing 15 were screened from multiple datasets and experimentally validated. Immune infiltration analyses showed fewer infiltrating adipocytes and endothelial cells in the lesioned versus preserved samples.
Our findings provide valuable information for future studies on the pathogenic mechanism of OA and potential therapeutic and diagnostic targets.
骨关节炎（OA）是一种退行性疾病，需要进一步研究。本研究比较了病变和未病变软骨下骨之间的基因表达和免疫浸润。使用多个组织数据集和实验对结果进行了验证。
在 GSE51588 数据集上鉴定 OA 患者病变和未病变胫骨平台之间的差异表达基因（DEGs）。此外，对病变和未病变侧进行功能注释和蛋白质-蛋白质相互作用（PPI）网络分析，以探索 OA 软骨下骨中的潜在治疗靶点。此外，还使用多种组织筛选共表达基因，并通过定量实时聚合酶链反应测量 OA 中鉴定出的候选 DEGs 的表达水平。最后，进行免疫浸润分析。
共鉴定出 1010 个 DEGs，其中 423 个上调，587 个下调。上调基因的生物学过程（BP）术语包括“骨骼系统发育”、“姐妹染色单体凝聚”和“骨化”。通路富集在“Wnt 信号通路”和“癌症中的蛋白聚糖”。下调基因的 BP 术语包括“炎症反应”、“外源性代谢过程”和“炎症反应的正调控”。富集的途径包括“神经活性配体-受体相互作用”和“AMP 激活蛋白激酶信号”。JUN、肿瘤坏死因子和白细胞介素-1 是 PPI 网络中的枢纽基因。从多个数据集筛选出胶原 XI A1 和富含亮氨酸重复序列 15 并进行了实验验证。免疫浸润分析显示病变样本中浸润的脂肪细胞和内皮细胞较少。
我们的研究结果为 OA 发病机制的进一步研究以及潜在的治疗和诊断靶点提供了有价值的信息。
