Classification of distinct osteoarthritis subtypes with different knee joint tissues by gene expression profiles.

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Bone & Joint Research Pub Date : 2023-12-01 DOI:10.1302/2046-3758.1212.BJR-2023-0021.R2
Yuan Xue, Liang Zhou, Jiaqian Wang
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Abstract

Aims: Knee osteoarthritis (OA) involves a variety of tissues in the joint. Gene expression profiles in different tissues are of great importance in order to understand OA.

Methods: First, we obtained gene expression profiles of cartilage, synovium, subchondral bone, and meniscus from the Gene Expression Omnibus (GEO). Several datasets were standardized by merging and removing batch effects. Then, we used unsupervised clustering to divide OA into three subtypes. The gene ontology and pathway enrichment of three subtypes were analyzed. CIBERSORT was used to evaluate the infiltration of immune cells in different subtypes. Finally, OA-related genes were obtained from the Molecular Signatures Database for validation, and diagnostic markers were screened according to clinical characteristics. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the effectiveness of markers.

Results: C1 subtype is mainly concentrated in the development of skeletal muscle organs, C2 lies in metabolic process and immune response, and C3 in pyroptosis and cell death process. Therefore, we divided OA into three subtypes: bone remodelling subtype (C1), immune metabolism subtype (C2), and cartilage degradation subtype (C3). The number of macrophage M0 and activated mast cells of C2 subtype was significantly higher than those of the other two subtypes. COL2A1 has significant differences in different subtypes. The expression of COL2A1 is related to age, and trafficking protein particle complex subunit 2 is related to the sex of OA patients.

Conclusion: This study linked different tissues with gene expression profiles, revealing different molecular subtypes of patients with knee OA. The relationship between clinical characteristics and OA-related genes was also studied, which provides a new concept for the diagnosis and treatment of OA.

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不同膝关节组织的不同骨关节炎亚型的基因表达谱分类。
目的:膝关节骨性关节炎(OA)涉及关节的多种组织。不同组织中的基因表达谱对了解OA具有重要意义。方法:首先,我们从gene expression Omnibus (GEO)获得软骨、滑膜、软骨下骨和半月板的基因表达谱。几个数据集通过合并和去除批处理效果来标准化。然后,我们使用无监督聚类将OA划分为三个亚型。分析了三种亚型的基因本体和途径富集情况。采用CIBERSORT法评价不同亚型免疫细胞的浸润情况。最后从分子特征数据库中获取oa相关基因进行验证,并根据临床特征筛选诊断标记物。采用定量反转录聚合酶链反应(qRT-PCR)验证标记的有效性。结果:C1亚型主要集中在骨骼肌器官的发育过程中,C2亚型参与代谢过程和免疫反应,C3亚型参与焦亡和细胞死亡过程。因此,我们将OA分为三个亚型:骨重塑亚型(C1)、免疫代谢亚型(C2)和软骨降解亚型(C3)。C2亚型巨噬细胞M0和活化肥大细胞数量明显高于其他两种亚型。COL2A1在不同亚型中存在显著差异。COL2A1的表达与年龄有关,转运蛋白颗粒复合物亚基2的表达与OA患者的性别有关。结论:本研究将不同组织与基因表达谱联系起来,揭示了膝关节OA患者不同的分子亚型。研究了临床特征与OA相关基因的关系,为OA的诊断和治疗提供了新的思路。
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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