Delineating the synovial fluid proteome: Recent advancements and ongoing challenges in biomarker research

There is an urgent need for identifying novel serum biomarkers that can be used to improve diagnosis, predict disease progression or response to therapy, or serve as therapeutic targets for rheumatic diseases. Synovial fluid (SF) is secreted by and remains in direct contact with the synovial membrane, and can reflect the biochemical state of the joint under different physiological and pathological conditions. Therefore, SF is regarded as an excellent source for identifying biomarkers of rheumatologic diseases. The use of high-throughput and/or quantitative proteomics and sophisticated computational software applied to analyze the protein content of SF has been well-adopted as an approach to finding novel arthritis biomarkers. This review will focus on some of the potential pitfalls of biomarker studies using SF, summarize the status of the field of SF proteomics in general, as well as discuss some of the most promising biomarker study approaches using proteomics. A brief status of the biomarker discovery efforts in rheumatoid arthritis, osteoarthritis and juvenile idiopathic arthritis is also provided.