Identification of a Panel of Novel Serum Osteoarthritis Biomarkers

Abstract

Osteoarthritis (OA) is the most common rheumatic pathology. Because currently available diagnostic methods are limited and lack sensitivity, the identification of new specific biological markers for OA has become a focus. The purpose of this study was to identify novel protein biomarkers for moderate and severe OA in serum. Sera were obtained from 50 moderate OA patients, 50 severe OA patients, and 50 nonsymptomatic controls. Serum protein levels were analyzed using isobaric tags for relative and absolute quantitation (iTRAQ) and matrix-assisted laser desorption/ionization (MALDI)-TOF/TOF mass spectrometry. We identified 349 different proteins in the sera, 262 of which could be quantified by calculation of their iTRAQ ratios. Three sets of proteins were significantly (p < 0.05) changed in OA samples compared to controls. Of these, 6 were modulated only in moderate OA, 13 only in severe OA and 7 in both degrees. Although some of these proteins, such as cartilage oligomeric matrix protein, have a previously reported putative biomarker value for OA, most are novel biomarker candidates for the disease. These include some complement components, lipoproteins, von Willebrand factor, tetranectin, and lumican. The specificity and selectivity of these candidates need to be validated before new molecular diagnostic or prognostic tests for OA can be developed.

Emerging targets in osteoarthritis therapy

“…Complement proteins are additional candidates detected in synovial fluids of OA patients by proteomic analysis [39,54,73,74]. DAMPs, including COMP, fibromodulin, the collagen XI NC4 domain, and the C-type lectin of the aggrecan G3 domain, can activate complement pathways [75,76].…”

Recent advances in the understanding of molecular mechanisms of cartilage degeneration, synovitis and subchondral bone changes in osteoarthritis

“…Tarkowski et al observed expression of decay accelerating factor (DAF) in the synovial lining cell layer in OA along with C5b-9 terminal complement complex suggesting activation of a complement-mediated response (96,97). However, blood or serum leaking into the joint after injury provide a source of complement proteins in many patients (98)(99)(100)(101), and as early as 1988, Corvetta et al found complement deposition in synovial membranes following meniscal tears or cartilage degeneration (102). Chondrocytes and synovial macrophages may also actively produce complement components and inhibitors (97,103).…”

Pharmacoproteomic Study of Three Different Chondroitin Sulfate Compounds on Intracellular and Extracellular Human Chondrocyte Proteomes

“…In this step, an average of 1200 spots were matched between the gels, and the average relative abundances were calculated. We considered changes within a 95% confidence interval (p Յ 0.05) and standardized average spot volume ratios exceeding 1.2 with a statistical power of Ͼ0.8, based on previous experience by our group (13,17,18). This analysis resulted in the detection of 46 spots significantly and reproducibly altered: 27 modulated by CS1, 4 by CS2, and 15 by CS3.…”