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

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.

Keywords: Label-free quantitative proteomics; Periprosthetic bone tissue; Periprosthetic joint infection; Staphylococcus aureus.