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CX3CR1在骨关节炎中的作用及生物标志物潜力的实验研究

Experimental study on the role and biomarker potential of CX3CR1 in osteoarthritis.

作者信息

Huang Junpu, Zheng Xifan, Meng Jinzhi, Wang Hongtao, Chen Lingyun, Yao Jun

机构信息

Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

The Second Clinical Medical College of Guangxi Medical University, Nanning, Guangxi, China.

出版信息

Ann Med. 2025 Dec;57(1):2529577. doi: 10.1080/07853890.2025.2529577. Epub 2025 Jul 11.

DOI:10.1080/07853890.2025.2529577
PMID:40641371
Abstract

BACKGROUND

Osteoarthritis (OA) is a chronic joint disorder marked by progressive degeneration of articular cartilage and the formation of secondary osteophytes. Despite extensive research, the underlying molecular mechanisms remain poorly understood. This study aimed to identify OA-associated genes and elucidate the molecular pathways implicated, with the goal of discovering reliable diagnostic biomarkers.

METHODS

The microarray dataset was retrieved from the Gene Expression Omnibus (GEO) and analyzed using R software to identify the signature gene, CX3CR1. Differentially expressed genes (DEGs) correlated with CX3CR1 were subsequently subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and immune infiltration analyses. A ceRNA regulatory network was also constructed. Vali-dation of CX3CR1 expression was conducted through qRT-PCR, Western blotting, and immunohistochemistry.

RESULTS

CX3CR1 emerged as a candidate gene significantly associated with OA, exhibiting regulatory roles primarily in lipid metabolism-related and extra-cellular matrix-related biological processes and signaling cascades. The infiltration levels of immune cells, particularly activated mast cells, appeared to modulate OA progression. Both and experiments demonstrated elevated CX3CR1 expression in OA tissues relative to controls, with a robust positive correlation observed between CX3CR1 and MMP13 levels.

CONCLUSION

CX3CR1 represents a potential biomarker for OA diagnosis and therapeutic targeting, exerting its effects by modulating lipid metabolism, extracellular matrix dynamics, and immune cell infiltration.

摘要

背景

骨关节炎(OA)是一种慢性关节疾病,其特征为关节软骨进行性退变和继发性骨赘形成。尽管进行了广泛研究,但其潜在分子机制仍了解甚少。本研究旨在鉴定与OA相关的基因并阐明其中涉及的分子途径,以期发现可靠的诊断生物标志物。

方法

从基因表达综合数据库(GEO)中检索微阵列数据集,并使用R软件进行分析以鉴定特征基因CX3CR1。随后,对与CX3CR1相关的差异表达基因(DEGs)进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)及免疫浸润分析。还构建了ceRNA调控网络。通过qRT-PCR、蛋白质免疫印迹和免疫组织化学对CX3CR1表达进行验证。

结果

CX3CR1作为与OA显著相关的候选基因出现,主要在脂质代谢相关和细胞外基质相关的生物学过程及信号级联反应中发挥调控作用。免疫细胞的浸润水平,尤其是活化的肥大细胞,似乎可调节OA进展。qRT-PCR和蛋白质免疫印迹实验均表明,与对照组相比,OA组织中CX3CR1表达升高,且CX3CR1与MMP13水平之间存在强正相关。

结论

CX3CR1代表一种潜在的OA诊断和治疗靶点生物标志物,通过调节脂质代谢、细胞外基质动态变化和免疫细胞浸润发挥作用。

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