FGA can be used as a promising therapeutic target in osteoarthritis.

Abstract

Background: This study aims to identify critical signaling pathways and pathogenic genes involved in osteoarthritis (OA) to provide a foundation for identifying targeted therapeutic strategies.

Methods: Twenty-six patients who underwent knee joint surgery in the Department of Orthopedics between January and December 2023 were enrolled. Cartilage samples in the experimental group (OA group) were harvested from the articular surfaces of the knee joints of OA patients undergoing total knee arthroplasty (TKA). In contrast, control samples were obtained from non-load-bearing regions of irreparable cartilage fragments excised during surgical management of tibial plateau fractures. Proteomic profiling was conducted using label-free quantitative mass spectrometry-based proteomics. Subsequent bioinformatics analysis was performed using R version 4.3.3 to identify differentially expressed proteins and key pathogenic genes. Quantitative real-time polymerase chain reaction (qPCR) and western blots were employed to validate the expression levels of candidate genes.

Results: The proteomic analysis revealed that regulatory signaling pathway of insulin-like growth factor-binding protein (IGFBP) for IGF transport and uptake and the platelet degranulation signaling pathway were significantly implicated in OA pathogenesis. Among the differentially expressed proteins, fibrinogen alpha chain (FGA) was identified as a central gene associated with OA. The qPCR and western blots validation confirmed significantly elevated expression of FGA in OA articular chondrocytes samples compared to controls.

Conclusions: FGA plays a pivotal role in the molecular pathology of OA and may represent a promising therapeutic target for the development of precision treatments for OA.