Proteomics and metabolomics studies in pigmented villonodular synovitis uncover the regulation of monocyte differentiation by the ADGRE5-NF-κB pathway

A total of 156 DEPs and 62 differential metabolites were identified. The "Osteoclast differentiation signalling" and "Nuclear factor-κB (NF-κB) survival signalling" pathways were significantly upregulated in PVNS samples, with Tumor Necrosis Factor Superfamily Member 11 (TNFSF11), Cathepsin K (CTSK), Adhesion G Protein-Coupled Receptor E5 (ADGRE5), and NF-κB showing marked increases in expression. Metabolomic analysis revealed that "Linoleic acid metabolism" and "Biosynthesis of unsaturated fatty acids" pathways were enhanced in PVNS, with metabolites such as 13-L-Hydroperoxylinoleic acid and 13-OxoODE being highly expressed. Western blot validation confirmed the elevated levels of ADGRE5, TNFSF11, CTSK, and NF-κB, suggesting a link between enhanced energy metabolism, lipid oxidation, and osteoclast differentiation. CONCLUSIONS: This study highlights the critical role of metabolic adaptations and immune cell activity in the progression of PVNS. The findings suggest that targeting ADGRE5 and NF-κB could offer new therapeutic strategies for controlling disease progression and reducing joint destruction in PVNS patients. Further research is needed to elucidate this disease's specific regulatory mechanisms and cell types.