Dr. Crow owns stock or stock options in Pfizer and Johnson & Johnson.
Proteomic Analysis of Synovial Fluid From the Osteoarthritic Knee: Comparison With Transcriptome Analyses of Joint Tissues
Version of Record online: 28 MAR 2013
Copyright © 2013 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 65, Issue 4, pages 981–992, April 2013
How to Cite
Ritter, S. Y., Subbaiah, R., Bebek, G., Crish, J., Scanzello, C. R., Krastins, B., Sarracino, D., Lopez, M. F., Crow, M. K., Aigner, T., Goldring, M. B., Goldring, S. R., Lee, D. M., Gobezie, R. and Aliprantis, A. O. (2013), Proteomic Analysis of Synovial Fluid From the Osteoarthritic Knee: Comparison With Transcriptome Analyses of Joint Tissues. Arthritis & Rheumatism, 65: 981–992. doi: 10.1002/art.37823
- Issue online: 28 MAR 2013
- Version of Record online: 28 MAR 2013
- Accepted manuscript online: 11 FEB 2013 03:20PM EST
- Manuscript Accepted: 4 DEC 2012
- Manuscript Received: 4 APR 2012
- NIH. Grant Numbers: T32-AR-007530-26, K08-AR-057859, R01-AG-022021, R21-AR-054887, K08-AR-054859
- Hospital for Special Surgery (Frankenthaler Fellowship in Restorative Mobility)
- Burroughs Wellcome Fund (Career Award)
The pathophysiology of the most common joint disease, osteoarthritis (OA), remains poorly understood. Since synovial fluid (SF) bathes joint cartilage and synovium, we reasoned that a comparative analysis of its protein constituents in health and OA could identify pathways involved in joint damage. We undertook this study to perform a proteomic analysis of knee SF from OA patients and control subjects and to compare the results to microarray expression data from cartilage and synovium.
Age-matched knee SF samples from 10 control subjects, 10 patients with early-stage OA, and 10 patients with late-stage OA were compared using 2-dimensional difference-in-gel electrophoresis and mass spectrometry (MS). MS with a multiplexed peptide selected reaction monitoring assay was used to confirm differential expression of a subset of proteins in an independent OA patient cohort. Proteomic results were analyzed by Ingenuity Pathways Analysis and compared to published synovial tissue and cartilage messenger RNA profiles.
Sixty-six proteins were differentially present in healthy and OA SF. Three major pathways were identified among these proteins: the acute-phase response signaling pathway, the complement pathway, and the coagulation pathway. Differential expression of 5 proteins was confirmed by selected reaction monitoring assay. A focused analysis of transcripts corresponding to the differentially present proteins indicated that both synovial and cartilage tissues may contribute to the OA SF proteome.
Proteins involved in the acute-phase response signaling pathway, the complement pathway, and the coagulation pathway are differentially regulated in SF from OA patients, suggesting that they contribute to joint damage. Validation of these pathways and their utility as biomarkers or therapeutic targets in OA is warranted.