University of Rochester
Grant: $213,616 - National Institutes of Health - Sep. 18, 2009
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Award Description: The administrative supplement funding will be used to develop a novel near infrared imaging method to quantify lymphatic draining function in the joint tissues of murine models of arthritis and to examine if improved lymphatic flow could reduce the joint inflammation and bone erosion in arthritic joints. The results will greatly accelerate the progress of the parent grant by providing a new technique and data regarding the possible impact of accelerated lymphangiogenesis on rheumatic pathology, studies which are within the scope of the origanl application, but not proposed.
Project Description: To develop a in vivo imaging method for longitudinally assess the lymphatic flow in mouse model of inflammatory arthritis and determine the effect of increasing lymphangiogenesis on the pathogenesis of arthritis. Rheumatoid arthritis is characterized by joint inflammation and bone erosion, which is accompanied by increased osteoclast formation and activity. Recent studies indicate that osteoclasts not only resorb bones but also produce factors that affect the function of other cell types. We found that osteoclasts and precursors release VEGF-C, a potent lymphatic factor, in reponse to TNF and RANKL, leading to the hypothesis of the parent grant: osteoclasts and precursors contribute to the pathogenesis of arthritis by affecting osteoclastogenesis and lymphangiogenesis. During the studies in the parent grant, we demonstrated that the blockage of lymphangiogenesis increases the severity of synovitis and reduces lymphatic drainage to local lymph nodes, suggesting a significant role of the lymphatic system in joint homeostasis during the development of inflammatory arthritis because. However, one technical obstacle to testing this hypothesis is the absence of non-invasive methods to assess changes in lymphatic draining function in vivo. The aim of this supplemental application is to develop a novel near infrared imaging method to quantify lymphatic draining function in the joint tissues of the murine model of inflammatory arthritis (Specific aim 1). Using this technique, we will examine if improved lymphatic flow could reduce the joint inflammation and bone erosion in arthritic joints (Specific aim 2). The results will greatly accelerate the progress of the parent grant by providing a new technique and data regarding the possible impact of accelerated lymphangiogenesis on rheumatic pathology, studies which are within the scope of the origanl application, but not proposed.
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Project Status: Less Than 50% Completed
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