Abstract
Biomarkers, especially biochemical markers, are important in osteoarthritis (OA) research, clinical trials, and drug development and have potential for more extensive use in therapeutic monitoring. However, they have not yet had any significant impact on disease diagnosis and follow-up in a clinical context. Nevertheless, the development of immunoassays for the detection and measurement of biochemical markers in OA research and therapy is an active area of research and development. The evaluation of biochemical markers representing low-grade inflammation or extracellular matrix turnover may permit OA prognosis and expedite the development of personalized treatment tailored to fit particular disease severities. However, currently detection methods have failed to overcome specific hurdles such as low biochemical marker concentrations, patient-specific variation, and limited utility of single biochemical markers for definitive characterization of disease status. These challenges require new and innovative approaches for development of detection and quantification systems that incorporate clinically relevant biochemical marker panels. Emerging platforms and technologies that are already on the way to implementation in routine diagnostics and monitoring of other diseases could potentially serve as good technological and strategic examples for better assessment of OA. State-of-the-art technologies such as advanced multiplex assays, enhanced immunoassays, and biosensors ensure simultaneous screening of a range of biochemical marker targets, the expansion of detection limits, low costs, and rapid analysis. This paper explores the implementation of such technologies in OA research and therapy. Application of novel immunoassay-based technologies may shed light on poorly understood mechanisms in disease pathogenesis and lead to the development of clinically relevant biochemical marker panels. More sensitive and specific biochemical marker immunodetection will complement imaging biomarkers and ensure evidence-based comparisons of intervention efficacy. We discuss the challenges hindering the development, testing, and implementation of new OA biochemical marker assays utilizing emerging multiplexing technologies and biosensors.
Highlights
Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and chronic disability in older individuals [1]
Large animals screened for OA biomarkers exhibit increased levels of matrix-degrading enzymes and extracellular matrix (ECM) fragments (MMP2, cartilage oligomeric matrix protein (COMP), and CTXII), associated with early stages of the disease, while cytokines emerge in the circulation at latter stages, which resembles some of the findings reported for human cohorts [77]
Similar quantitative expression patterns were determined for 13 plasma antigens common to both platforms, while the potential efficacy of proximity extension assay was endorsed, as it only demonstrated that the expression of CEA, IL-8, and prolactin are significantly correlated with colorectal cancer stage
Summary
Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and chronic disability in older individuals [1]. It is evident that biochemical marker research in cancer is highly advanced compared to other disease areas, and these studies may serve as good examples of simplified ways for sensitive and specific detection of different cancer types, for instance breast, colorectal, etc Such state-of-the art technologies as multiplexing a combination of biochemical markers and implementation of biosensors save time and resources for the prediction of treatment response. Different inflammatory biochemical marker combinations may represent OA lesions of different joints These data support findings from an earlier pilot study in human knee synovial fluid [118], showing that among 21 cytokines screened, elevated MCP-1 and MIP-1 in SF were increased in subjects with advanced arthritis, based on the International Cartilage Repair Society (ICRS) criteria. The panel of metabolic products of cartilage and bone ECM molecules, representing the processes of breakdown (catabolism) or synthesis (anabolism), has been
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