Presentation Abstract

Session: 571-585-Shoulder and Elbow IV
Date/Time: Friday, Mar 22, 2013, 9:42 AM - 9:48 AM
Location McCormick Place, Room N427
Presentation Number: Paper 584
Title: Proteomic Analysis of Shoulder Osteoarthritis
Classification: +Basic Science/Biologics (Shoulder/Elbow)
Keywords: Shoulder Basic Science / Biomechanics
Author(s): John Paul Wanner, BS, Wauwatosa, Wisconsin
Roopa Shree Subbaiah, PhD, Cleveland, Ohio
Yousef Shishani, MD, Cleveland, Ohio
Olena Skomorovska-Prokvolit, PhD, Cleveland, Ohio
Robert J. Gillespie, MD, Shaker Heights, Ohio
Eric Boilard, PhD, Quebec City, Canada
Sujatha Mohan, Yokohama, Japan
Masaru Miyagi, Cleveland, New York
Reuben Gobezie, MD, Cleveland, Ohio
Abstract: INTRODUCTION: Currently, the development of effective treatments for osteoarthritis (OA) has been hampered by a poor understanding of OA at the molecular and cellular levels. Emerging as a disease of the ‘whole joint,’ the importance of the biochemical interplay of various tissues including synovium, bone and articular cartilage is becoming increasingly significant. Bathing the entire joint structure, the proteomic analysis of synovial fluid (SF) offers a snapshot of the biologic environment throughout disease progression. The purpose of this study was to examine the proteome of SF in osteoarthritic shoulders at varying stages of OA progression to identify dysregulated signaling pathways and sensitive biomarkers.
METHODS: A cross-sectional study of 17 patients with early OA (n=5), late OA (n=5) and control individuals (n=7) was conducted. Low abundant proteins were quantitatively analyzed in each of the experimental groups and compared to the pooled control samples using 18O labeling and tandem mass spectrometry. Database search was performed for low abundant proteins while analysis of high abundant proteins was achieved using in-gel digestion. Normalization was performed within and across biological replicates. Cytokine profiling of synovial fluid was also performed and dysregulated pathways were identified using Ingenuity pathway analysis.
RESULTS: Across the biological replicates, 106 and 118 proteins were found to be similar within the early and late subgroups respectively with 34 and 40 found to be differentially expressed (fold change ≥1.5 and ≤ -1.5). Data validation of aggrecan core protein, fibrinogen, tenascin and complement factor D was performed by Western blot which confirmed mass spectrometry results. Networks related to “Lipid metabolism, Molecular transport, Small Molecule Biochemistry” were down-regulated in both early and late OA sets while inflammatory cytokines Interleukin 6, 8 and 18 were up-regulated in early and late OA.
DISCUSSION AND CONCLUSION: Pathway analysis suggests a strong wound signature in early and late OA. The observed increase in expression of complement molecules in both early and late OA continues to suggest an ongoing effort to seal the wound formed within the joint. Dysregulation of wound signaling pathways in shoulder arthritis reflects the presence of a ‘chronic wound’ which progresses irreversibly from early to later stages of OA.

Disclosures: Presenting Author
1 - Arthrex Inc.; 3B 5 - Arthrex Inc. Tornier; 7 - Saunders/Mosby-Elsevier
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