High abundance synovial fluid proteome: distinct profiles in health and osteoarthritis

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.

Proteomic characterization of mouse cartilage degradation in vitro

“…Gelsolin is underexpressed in human RA synovial tissue (36,40), and gelsolin down-regulation is associated with cytoskeletal remodeling in arthritis synovial fibroblasts (36,41). The abundance of actin and gelsolin along with many other cytoskeletal proteins in synovial fluid (4) suggests that gelsolin may serve an additional protective role in the synovium. Cytoskeletal rearrangement in arthritis cartilage and chondrocytes has been reported (6,42), but little is known about the mechanism.…”

“…The differential profiling of cartilage, synovial fluid, and serum from patients with arthritis, using proteomic methods such as multidimensional liquid chromatography or 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) in conjunction with mass spectrometry (MS), is increasingly being applied to identify novel mediators of pathology and markers for joint disease (2)(3)(4)(5). Human chondrocyte and cartilage cultures have also been used to identify pathologic changes associated with osteoarthritis (OA), using proteomic tech-niques (6,7).…”

Hyaluronan inhibits BMP‐induced osteoblast differentiation

“…OA is a chronic degenerative joint disorder, which is characterized by articular cartilage destruction and bone formation such as osteophyte formation and subchondral bone screlosis [34,35]. Since it has been reported that HA concentration of the joint is reduced in OA patients [36], HA may have therapeutic significance in OA patient by inhibiting bone formation.…”

Reaching Consensus and Highlighting Future Directions for Research: The Osteoarthritis Summit Breakout Sessions

“…Imaging cell death using Annexin V is a possibility, as are the use of DNA fragments and other available biomarkers (e.g., vimentin) [3]. Measurement of streaming potential in cartilage offers a precise and reproducible method of measuring proteoglycan content.…”