Wen Xianghui, Fang Linkai, Chen Zena, Liu Dong, Wen Shenghui, Li Jinwei, Li Qiuxia, Wei Qiujing, Cao Shuangyan, Zhang Peng, Gu Jieruo
Shenzhen Longhua District Central Hospital, Shenzhen, China.
Shenzhen Longhua Institute of Immunology Transformation, Shenzhen, China.
Front Med (Lausanne). 2025 May 14;12:1556118. doi: 10.3389/fmed.2025.1556118. eCollection 2025.
Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the axial skeleton and peripheral joints, with hip arthropathy representing a severe complication that critically impairs mobility. While persistent inflammation is a hallmark of AS, the molecular mechanisms driving hip involvement remain poorly characterized. This study aimed to identify and validate protein biomarkers associated with hip arthropathy progression in AS through integrated proteomic and functional analyses.
Liquid chromatography-mass spectrometry (LC-MS/MS) was employed to screen for differentially abundant proteins (DAPs) in hip joint tissues from 30 AS patients and 14 non-AS controls. Bioinformatics methods were utilized to screen for and identify key DAPs.
A total of 2,050 proteins were relatively quantified, with 109 DAPs (34 upregulated and 75 downregulated) meeting the criteria of < 0.05 and a fold change ≥1.5 or ≤0.67. Enriched GO terms represented by DAPs included the Wnt signaling pathway, MAPK cascade, and antigen processing and presentation of exogenous peptide antigen via MHC class I. The main Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included the PI3K-Akt signaling pathway, ribosome, metabolic pathways, and neutrophil extracellular trap formation. The protein-protein interaction (PPI) network identified ribosomal proteins (RPs), including RPS11, RPS24, RPL35, RPS3A, RPS6, RPS8, RPS14, and RPS7, as highly connected hub proteins. These RPs were significantly enriched in pathways associated with hip arthropathy pathogenesis, particularly osteoblast differentiation and T cell-mediated immune regulation.
Based on proteomics approaches and bioinformatics analysis, this study discovered DAPs and signaling pathways associated with hip arthropathy in AS. It may provide potential as screening tools or therapeutic targets for AS, warranting further research for validation.
强直性脊柱炎(AS)是一种主要影响中轴骨骼和外周关节的慢性炎症性疾病,髋关节病是一种严重并发症,会严重损害活动能力。虽然持续炎症是AS的一个标志,但驱动髋关节受累的分子机制仍不清楚。本研究旨在通过综合蛋白质组学和功能分析,鉴定和验证与AS患者髋关节病进展相关的蛋白质生物标志物。
采用液相色谱-质谱联用(LC-MS/MS)技术筛选30例AS患者和14例非AS对照者髋关节组织中差异丰富蛋白(DAPs)。利用生物信息学方法筛选和鉴定关键DAPs。
共相对定量了2050种蛋白质,其中109种DAPs(34种上调和75种下调)符合标准(<0.05,倍数变化≥1.5或≤0.67)。DAPs富集的基因本体(GO)术语包括Wnt信号通路、丝裂原活化蛋白激酶(MAPK)级联反应以及通过MHC I类对外源肽抗原进行抗原加工和呈递。主要的京都基因与基因组百科全书(KEGG)通路包括磷脂酰肌醇3激酶-蛋白激酶B(PI3K-Akt)信号通路、核糖体、代谢通路和中性粒细胞胞外陷阱形成。蛋白质-蛋白质相互作用(PPI)网络确定核糖体蛋白(RPs),包括核糖体蛋白S11(RPS11)、核糖体蛋白S24(RPS24)、核糖体蛋白L35(RPL35)、核糖体蛋白S3A(RPS3A)、核糖体蛋白S6(RPS6)、核糖体蛋白S8(RPS8)、核糖体蛋白S14(RPS14)和核糖体蛋白S7(RPS7),为高度连接的枢纽蛋白。这些RPs在与髋关节病发病机制相关的通路中显著富集,特别是在成骨细胞分化和T细胞介导的免疫调节方面。
基于蛋白质组学方法和生物信息学分析,本研究发现了与AS患者髋关节病相关的DAPs和信号通路。它可能为AS提供作为筛选工具或治疗靶点的潜力,值得进一步研究验证。