Abstract
The development of increasingly high-throughput and sensitive mass spectroscopy-based proteomic techniques provides new opportunities to examine the physiology and pathophysiology of many biologic fluids and tissues. The purpose of this study was to determine protein expression profiles of high-abundance synovial fluid (SF) proteins in health and in the prevalent joint disease osteoarthritis (OA). A cross-sectional study of 62 patients with early OA (n = 21), patients with late OA (n = 21), and control individuals (n = 20) was conducted. SF proteins were separated by using one-dimensional PAGE, and the in-gel digested proteins were analyzed by electrospray ionization tandem mass spectrometry. A total of 362 spots were examined and 135 high-abundance SF proteins were identified as being expressed across all three study cohorts. A total of 135 SF proteins were identified. Eighteen proteins were found to be significantly differentially expressed between control individuals and OA patients. Two subsets of OA that are not dependent on disease duration were identified using unsupervised analysis of the data. Several novel SF proteins were also identified. Our analyses demonstrate no disease duration-dependent differences in abundant protein composition of SF in OA, and we clearly identified two previously unappreciated yet distinct subsets of protein profiles in this disease cohort. Additionally, our findings reveal novel abundant protein species in healthy SF whose functional contribution to SF physiology was not previously recognized. Finally, our studies identify candidate biomarkers for OA with potential for use as highly sensitive and specific tests for diagnostic purposes or for evaluating therapeutic response.
Highlights
Osteoarthritis (OA), which is characterized by progressive destruction of articular cartilage, is by far the most common musculoskeletal disorder in the world, afflicting 40 million people in the USA alone [1,2]
Our data suggest that there is no significant change in the composition of high-abundance proteins between early and late OA, we identify distinct patterns of protein expression within OA patients that suggests identifiable subsets of disease that are independent of disease duration
18 proteins represented keratin species that we considered to be contaminants from the cutaneous puncture performed during arthrocentesis and so removed them from further consideration, leaving a total of 117 synovial fluid (SF) proteins identified
Summary
Osteoarthritis (OA), which is characterized by progressive destruction of articular cartilage, is by far the most common musculoskeletal disorder in the world, afflicting 40 million people in the USA alone [1,2]. A number of factors have frustrated efforts to elucidate the disease, and to develop diagnostic and treatment approaches; these include conflicting observations in epidemiologic studies, protracted disease duration, poorly correlated symptoms and radiographic findings, and lack of effective therapies Compounding these difficulties, experimental mouse models are lacking and diseased tissue for experimental analyses is typically obtained from patients with advanced disease at joint replacement surgery, thereby limiting insight to late stages of disease. The pathophysiology of disease involves the entire joint structure, including cartilage, synovium, ligaments, subchondral bone, and periarticular muscle Documented contributors to this pathophysiology include genetic predisposition, trauma, inflammation, and metabolic changes.
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