Protein classification and distribution in osteoarthritic human synovial tissue by matrix-assisted laser desorption...

The remodeling of the synovial membrane, which normally lubricates the joints by producing synovial fluid, is one of the most characteristic events in the pathology of osteoarthritis (OA). The heterogeneity and spatial distribution of proteins in the synovial membrane are poorly studied and we hypothesized that they constitute excellent molecular disease classifiers for the accurate diagnosis of the disease. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) allows for the study of the localization and identification of hundreds of different molecules with high sensitivity in very thin tissue sections. In this work, we employed MALDI-MSI in combination with principal component analysis and discriminant analysis to reveal the specific profile and distribution of digested proteins in human normal and OA synovial membranes. Proteins such as hemoglobin subunit alpha 2, hemoglobin subunit beta, actin aortic smooth muscle, biglycan, and fibronectin have been directly identified from human synovial biopsies. In addition, we have determined the location of disease-specific OA markers. Some of them which are located in areas of low inflammation provide valuable information on tissue heterogeneity. Finally, we described the OA molecular protein signatures common to synovial and other articular tissues such as cartilage. For the first time, normal and OA human synovial membranes have been classified by MALDI-MSI, thus offering a new sensitive tool for the study of rheumatic pathologies.