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通过无标记定量蛋白质组学分析假体周围关节感染患者的骨蛋白。

Bone protein analysis via label-free quantitative proteomics in patients with periprosthetic joint infection.

机构信息

Department of Orthopedic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Department of Orthopedic Surgery, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China.

出版信息

J Proteomics. 2022 Feb 10;252:104448. doi: 10.1016/j.jprot.2021.104448. Epub 2021 Dec 6.

DOI:10.1016/j.jprot.2021.104448
PMID:34883267
Abstract

Periprosthetic joint infection (PJI) is a catastrophic complication of arthroplasty. The treatment of PJI often requires multiple operations and long-term use of antibiotics, making PJI a substantial health and economic burden for patients. Therefore, there is an urgent need to elucidate the pathological mechanism of PJI to explore new therapeutic methods. This study aimed to explore proteomics changes in bone tissue around the prosthesis during PJI development, to explain the pathological mechanism and to provide new treatment ideas. Ten patients who underwent revision surgery at our institution were included: 5 patients with Staphylococcus aureus PJI and 5 patients with aseptic failure. The proteomics changes in bone tissues after PJI were investigated by label-free quantitative proteomics, and the pathways affected by the differential proteins were analyzed by GO annotation, GO enrichment analysis, KEGG enrichment analysis and protein-protein interaction network analysis. We identified 435 differentially expressed proteins (DEPs), with 213 upregulated and 222 downregulated proteins. Analysis revealed activation of immune-related pathways, such as complement and coagulation cascades, phagocytosis, and neutrophil activation, and inhibition of energy metabolism pathways represented by the TCA cycle. We also observed an altered balance between osteoblasts and osteoclasts during S. aureus PJI. We hope that these processes will reveal new treatment ideas. SIGNIFICANCE: PJI is a catastrophic complication of arthroplasty. When infection occurs, bacteria may invade periprosthetic bone tissue to escape immunity and cause damage. So far, only few studies focused on the changes of proteomics associated to PJI. This is the first study to describe the proteomics changes of periprosthetic bone tissue of patients with PJI. We found that the pathological process of S. aureus PJI mainly involves activation of the immune system, decreased energy metabolism, and an altered balance of osteoblasts and osteoclasts.

摘要

假体周围关节感染(PJI)是关节置换术的灾难性并发症。PJI 的治疗通常需要多次手术和长期使用抗生素,这使得 PJI 给患者带来了巨大的健康和经济负担。因此,迫切需要阐明 PJI 的病理机制,以探索新的治疗方法。本研究旨在探讨 PJI 发展过程中假体周围骨组织的蛋白质组学变化,以解释病理机制并提供新的治疗思路。本研究纳入了在我院接受翻修手术的 10 名患者:5 名金黄色葡萄球菌 PJI 患者和 5 名无菌性失败患者。通过无标记定量蛋白质组学研究 PJI 后骨组织的蛋白质组学变化,并通过 GO 注释、GO 富集分析、KEGG 富集分析和蛋白质-蛋白质相互作用网络分析分析受差异蛋白影响的途径。我们鉴定出 435 个差异表达蛋白(DEPs),其中 213 个上调,222 个下调。分析显示,免疫相关途径(如补体和凝血级联、吞噬作用和中性粒细胞激活)被激活,同时能量代谢途径(如 TCA 循环)受到抑制。我们还观察到金黄色葡萄球菌 PJI 期间成骨细胞和破骨细胞之间的平衡发生改变。我们希望这些过程将揭示新的治疗思路。意义:PJI 是关节置换术的灾难性并发症。当感染发生时,细菌可能会侵入假体周围的骨组织以逃避免疫并造成损伤。到目前为止,只有少数研究关注与 PJI 相关的蛋白质组学变化。这是第一项描述 PJI 患者假体周围骨组织蛋白质组学变化的研究。我们发现,金黄色葡萄球菌 PJI 的病理过程主要涉及免疫系统的激活、能量代谢的降低以及成骨细胞和破骨细胞平衡的改变。

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