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Abstract：
UNASSIGNED: This study seeks to identify potential clinical biomarkers for osteoarthritis (OA) using bioinformatics and investigate OA mechanisms through cellular assays.
UNASSIGNED: Differentially Expressed Genes (DEGs) from GSE52042 (four OA samples, four control samples) were screened and analyzed with protein-protein interaction (PPI) analysis. Overlapping genes in GSE52042 and GSE206848 (seven OA samples, and seven control samples) were identified and evaluated using Gene Set Enrichment Analysis (GSEA) and clinical diagnostic value analysis to determine the hub gene. Finally, whether and how the hub gene impacts LPS-induced OA progression was explored by in vitro experiments, including Western blotting (WB), co-immunoprecipitation (Co-IP), flow cytometry, etc.
UNASSIGNED: Bioinformatics analysis of DEGs (142 up-regulated and 171 down-regulated) in GSE52042 identified two overlapping genes (U2AF2, TPX2) that exhibit significant clinical diagnostic value. These genes are up-regulated in OA samples from both GSE52042 and GSE206848 datasets. Notably, TPX2, which AUC = 0.873 was identified as the hub gene. In vitro experiments have demonstrated that silencing TPX2 can alleviate damage to chondrocytes induced by lipopolysaccharide (LPS). Furthermore, there is a protein interaction between TPX2 and MMP13 in OA. Excessive MMP13 can attenuate the effects of TPX2 knockdown on LPS-induced changes in OA protein expression, cell growth, and apoptosis.
UNASSIGNED: In conclusion, our findings shed light on the molecular mechanisms of OA and suggested TPX2 as a potential therapeutic target. TPX2 could promote the progression of LPS-induced OA by up-regulating the expression of MMP13, which provides some implications for clinical research.
UNASSIGNED: Differentially Expressed Genes (DEGs) from GSE52042 (four OA samples, four control samples) were screened and analyzed with protein-protein interaction (PPI) analysis. Overlapping genes in GSE52042 and GSE206848 (seven OA samples, and seven control samples) were identified and evaluated using Gene Set Enrichment Analysis (GSEA) and clinical diagnostic value analysis to determine the hub gene. Finally, whether and how the hub gene impacts LPS-induced OA progression was explored by in vitro experiments, including Western blotting (WB), co-immunoprecipitation (Co-IP), flow cytometry, etc.
UNASSIGNED: Bioinformatics analysis of DEGs (142 up-regulated and 171 down-regulated) in GSE52042 identified two overlapping genes (U2AF2, TPX2) that exhibit significant clinical diagnostic value. These genes are up-regulated in OA samples from both GSE52042 and GSE206848 datasets. Notably, TPX2, which AUC = 0.873 was identified as the hub gene. In vitro experiments have demonstrated that silencing TPX2 can alleviate damage to chondrocytes induced by lipopolysaccharide (LPS). Furthermore, there is a protein interaction between TPX2 and MMP13 in OA. Excessive MMP13 can attenuate the effects of TPX2 knockdown on LPS-induced changes in OA protein expression, cell growth, and apoptosis.
UNASSIGNED: In conclusion, our findings shed light on the molecular mechanisms of OA and suggested TPX2 as a potential therapeutic target. TPX2 could promote the progression of LPS-induced OA by up-regulating the expression of MMP13, which provides some implications for clinical research.
摘要：
■本研究旨在使用生物信息学鉴定骨关节炎（OA）的潜在临床生物标志物，并通过细胞测定研究OA机制。
■来自GSE52042（四个OA样本，四个对照样品）进行筛选，并通过蛋白质-蛋白质相互作用（PPI）分析进行分析。GSE52042和GSE206848中的重叠基因（七个OA样品，和七个对照样品）进行鉴定，并使用基因集富集分析（GSEA）和临床诊断价值分析进行评估，以确定hub基因。最后,通过体外实验探索了hub基因是否以及如何影响LPS诱导的OA进展，包括蛋白质印迹（WB），免疫共沉淀（Co-IP），流式细胞术,等。
■对GSE52042中的DEGs（142个上调和171个下调）的生物信息学分析确定了两个重叠基因（U2AF2，TPX2），它们具有显着的临床诊断价值。这些基因在来自GSE52042和GSE206848数据集的OA样品中上调。值得注意的是,TPX2,其AUC=0.873被鉴定为hub基因。体外实验表明，沉默TPX2可以减轻脂多糖（LPS）诱导的软骨细胞损伤。此外，在OA中TPX2和MMP13之间存在蛋白质相互作用。过量的MMP13可以减弱TPX2敲低对LPS诱导的OA蛋白表达变化的影响。细胞生长,和凋亡。
■总而言之，我们的研究结果阐明了OA的分子机制,并提示TPX2是一个潜在的治疗靶点.TPX2可能通过上调MMP13的表达来促进LPS诱导的OA的进展，这为临床研究提供了一定的启示。
■来自GSE52042（四个OA样本，四个对照样品）进行筛选，并通过蛋白质-蛋白质相互作用（PPI）分析进行分析。GSE52042和GSE206848中的重叠基因（七个OA样品，和七个对照样品）进行鉴定，并使用基因集富集分析（GSEA）和临床诊断价值分析进行评估，以确定hub基因。最后,通过体外实验探索了hub基因是否以及如何影响LPS诱导的OA进展，包括蛋白质印迹（WB），免疫共沉淀（Co-IP），流式细胞术,等。
■对GSE52042中的DEGs（142个上调和171个下调）的生物信息学分析确定了两个重叠基因（U2AF2，TPX2），它们具有显着的临床诊断价值。这些基因在来自GSE52042和GSE206848数据集的OA样品中上调。值得注意的是,TPX2,其AUC=0.873被鉴定为hub基因。体外实验表明，沉默TPX2可以减轻脂多糖（LPS）诱导的软骨细胞损伤。此外，在OA中TPX2和MMP13之间存在蛋白质相互作用。过量的MMP13可以减弱TPX2敲低对LPS诱导的OA蛋白表达变化的影响。细胞生长,和凋亡。
■总而言之，我们的研究结果阐明了OA的分子机制,并提示TPX2是一个潜在的治疗靶点.TPX2可能通过上调MMP13的表达来促进LPS诱导的OA的进展，这为临床研究提供了一定的启示。
