The role of this project is to assess the role of anti-VEGF therapy in osteoarthritis (OA) progression and associated pain. We will assess the use of low dose intra-articular anti-VEGF antibody at the knee joint in a murine OA model, which will be created by destabilization of the medial meniscus (DMM). Intra-articular administration of anti-VEGF antibody will be tested at different time points of OA progression in different groups. We will assess the role of Hyasis(r) Link hydrogel as slow release agent for anti-VEGF antibody. We will selectively silence gene expression of VEGF at chondrocytes using VEGFfl/fl: Aggrecan-CreERT2 transgenic mice, to asses chondrocyte specific role of VEGF associated OA progression and pain. OA progression will be assessed by Safranin-O stained histologic imaging and OARSI scoring. Longitudinal pain behavior will be assessed by mechanical allodynia, using von Frey filament testing. Specific mediators of VEGF mediated OA progression and pain will be assessed by immunofluorescence imaging and immunohistochemistry at the joint surface, synovium, and dorsal root ganglia. Results of this study will assess the potential o anti-VEGF therapy as a disease modifying OA drug as well as potential for targeting OA associated pain.

Public Health Relevance

This study will assess the significance of VEGF in OA and associated pain. It will assess whether therapy with low dose intra-articular anti-VEGF antibody can be used to reduce OA progression and pain when administered at different time points. The study will evaluate Hyasis(r) Link hydrogel as a slow release agent for anti-VEGF antibody for OA treatment. Further, the role of chondrocyte VEGF expression in OA progression will be analyzed using VEGFfl/fl: Aggrecan-CreERT2 transgenic mice.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1-F10B-B (20)L)
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Tyree, Bernadette
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Rush University Medical Center
Schools of Medicine
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