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髌下脂肪垫的蛋白质组学和脂质组学图谱及其在膝骨关节炎中的临床意义。

Proteomic and lipidomic landscape of the infrapatellar fat pad and its clinical significance in knee osteoarthritis.

机构信息

Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China.

Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University (The First People's Hospital of Hefei), 390 Huaihe Road, Hefei 230061, Anhui, China; Department of Orthopedics, Bengbu Medical College, Bengbu City 233000, China.

出版信息

Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Aug;1869(6):159513. doi: 10.1016/j.bbalip.2024.159513. Epub 2024 May 22.

DOI:10.1016/j.bbalip.2024.159513
PMID:38788831
Abstract

Osteoarthritis (OA) is a prevalent joint disease that can be exacerbated by lipid metabolism disorders. The intra-articular fat pad (IFP) has emerged as an active participant in the pathological changes of knee OA (KOA). However, the proteomic and lipidomic differences between IFP tissues from KOA and control individuals remain unclear. Samples of IFP were collected from individuals with and without OA (n = 6, n = 6). Subsequently, these samples underwent liquid chromatography/mass spectrometry-based label-free quantitative proteomic and lipidomic analysis to identify differentially expressed proteins (DEPs) and lipid metabolites (DELMs). The DEPs were further subjected to enrichment analysis, and hub DEPs were identified using multiple algorithms. Additionally, an OA diagnostic model was constructed based on the identified hub DEPs or DELMs. Furthermore, CIBERSORT was utilized to investigate the correlation between hub protein expression and immune-related modules in IFP of OA. Our results revealed the presence of 315 DEPs and eight DELMs in IFP of OA patients compared to the control group. Enrichment analysis of DEPs highlighted potential alterations in pathways related to coagulation, complement, fatty acid metabolism, and adipogenesis. The diagnostic model incorporating four hub DEPs (AUC = 0.861) or eight DELMs (AUC = 0.917) exhibited excellent clinical validity for diagnosing OA. Furthermore, the hub DEPs were found to be associated with immune dysfunction in IFP of OA. This study presents a distinct proteomic and lipidomic landscape of IFP between individuals with OA and those without. These findings provide valuable insights into the molecular changes associated with potential mechanisms underlying OA.

摘要

骨关节炎(OA)是一种常见的关节疾病,其可被脂质代谢紊乱加重。关节内脂肪垫(IFP)已成为膝骨关节炎(KOA)病理变化的积极参与者。然而,KOA 和对照组 IFP 组织之间的蛋白质组学和脂质组学差异尚不清楚。收集 OA 患者和非 OA 患者(n=6,n=6)的 IFP 样本。随后,对这些样本进行基于液相色谱/质谱的无标记定量蛋白质组学和脂质组学分析,以鉴定差异表达蛋白(DEPs)和脂质代谢物(DELMs)。进一步对 DEPs 进行富集分析,并使用多种算法鉴定枢纽 DEPs。此外,基于鉴定的枢纽 DEPs 或 DELMs 构建 OA 诊断模型。进一步利用 CIBERSORT 分析 OA 患者 IFP 中枢纽蛋白表达与免疫相关模块之间的相关性。与对照组相比,OA 患者 IFP 中存在 315 个 DEPs 和 8 个 DELMs。DEPs 富集分析突出了与凝血、补体、脂肪酸代谢和脂肪生成相关的途径中的潜在改变。包含四个枢纽 DEPs 的诊断模型(AUC=0.861)或八个 DELMs(AUC=0.917)对 OA 的诊断具有优异的临床有效性。此外,枢纽 DEPs 与 OA 患者 IFP 中的免疫功能障碍有关。本研究呈现了 OA 患者和非 OA 患者 IFP 之间的独特蛋白质组学和脂质组学图谱。这些发现为 OA 潜在机制相关的分子变化提供了有价值的见解。

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