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Rebekah C. Brown Proteomic Analysis of Human Synovial Fluid, Synovium and Cartilage in Healthy and Osteoarthritic Subjects: An Investigation of the Knee Joint Rebekah C. Brown, Reuben Gobezie MD., James Crish Ph.D., Eldra Daniels, Eric Rodriguez, Mark Chance Ph.D., Gurkan Bebek Ph.D., Tim Henderson, Serguei Ilchenko Ph.D., Giri Gokulrandan Ph.D., Patrick Leahy Ph.D. and Chunbiao Li University Hospital Department of Orthopedics, Case Center for Proteomics and Bioinformatics, The Gene Expression and Genotyping Core Facility, Case Comprehensive Cancer Center, Case Western Reserve University Osteoarthritis is a multifactorial degenerative joint disease characterized by pathophysiologic changes to synovial joints. (e-medicine) Osteoarthritis (OA) of the knee joint is a huge problem affecting, approximately, 27% of people over the age of 45. [MD Consult Epidemiology of Osteoarthritis Rheumatic Diseases Clinics of North America - Volume 34, Issue 3 (August 2008)] The question to ask is how do we mitigate OA and its effects? Through proteomics, “[t]he study of the structure and function of proteins, including the way they work and interact with each other inside cells.” [www.cancer.gov], we can answer key questions; namely, what is the proteome of an arthritic individual’s synovium, synovial fluid, and cartilage; what are the biological pathway alterations between these tissues and disease states; and what is the molecular level of alteration(s) defining osteoarthritis? These questions were explored using several proteomic techniques and microarray analysis. The synovial fluid, synovium and cartilage samples were prepared from five individuals for 1-D PAGE electrophoresis with subsequent in-gel digestion and Western Blot analysis. The in-gel digestion products were analyzed by FT/LTQ and OrbiTRAP mass spectral analysis, MASCOT and MASRAN (MASCOT Results Analyzer) within the Case Center for Proteomics and Bioinformatics. Western Blot analysis was performed targeting the proteins Gelsolin and Afamin. RNA isolation procedures were performed in the Gobezie lab for microarray analysis at The Gene Expression and Genotyping Core Facility, Case Comprehensive Cancer Center. Analysis showed that there are proteomic differences between disease states. In synovial fluid, the proteome of the early osteoarthritis (EOA) group is greater than the healthy group, which was greater than the late osteoarthritis (LOA) group. The LOA proteome is greater than the EOA proteome in synovial tissue and cartilage. Additionally, within the same individual, the proteome differs between tissue types. The proteome is larger in synovium versus that of synovial fluid and cartilage. Preliminary microarray analysis results substantiate these proteomic results. Results are still pending regarding the biological pathway analysis. So far, it is evident that there are discrete protein alterations between healthy and osteoarthritic individuals. This knowledge of proteomic changes associated with OA can be translated into obtaining definitive diagnoses and earlier detection of the disease. Focusing on a proteomic approach to study osteoarthritis, such as biological pathway alteration, can potentially yield very insightful information about the arthritic process. Supported by NIH Heart, Lung and Blood Institute Grant: Ruth L. Kirschstein National Research Service Award Short-Term Institutional Research Training Grants (T35) 14
Lauren Cao Evaluation of cardiovascular disease risk profile in psoriasis patients by the use of pro-inflammatory surrogate markers of cardiovascular disease in CT scan, ultrasound and serum findings Lauren Cao, B.S., Rivka Feig and Neil Korman, MD/PhD Department of Dermatology, University Hospitals Case Medical Center Psoriasis is a recrudescing immune-mediated disease that affects 2% of U.S. population, with costs exceeding $1 billion. A growing literature suggests association of psoriasis with cardiovascular diseases (CVDs). The skin-driven vascular inflammation, propagated by elevated levels of pro-inflammatory S100A8/A9 and VEGF released from psoriatic plaques, may contribute to increased CVD risk seen in psoriasis. This cross-sectional study will assess the propensity of psoriasis patients to develop CVD compared to properly-selected controls, as measured by coronary artery calcification scoring (CACS) CT scan; carotid intima-media thickness (CIMT) and flow-mediated dilation (FMD) ultrasound results. We are stratifying by disease severity (moderate-severe, mild, control), age (>=40,
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