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Technology, Department of Molecular Biology and Pharmacology, St. Louis, MO, USA CD47 Integrin-Associated Protein ; is a five-transmembrane segment protein that is known to interact with L3 integrins. Previous studies in our lab revealed that L3 integrin deficient mice are protected from bone metastasis. This finding led us to evaluate tumor growth and bone metastasis in CD47 deficient mice. When we delivered B16 luciferase-labeled murine osteolytic melanoma cells directly into the mouse tibia, we observed decreased tumor growth in the CD47- mice compared to WT controls. As in the L3 mice, there was decreased tumor associated bone destruction in the CD47 mice compared with WT controls suggestive of a defect in osteoclast OC ; function. Thus we evaluated OC formation in the CD47 mice. The number of multinucleated TRAP-positive OCs formed by differentiating bone marrow macrophages with MCSF and RANKL was decreased in CD47 mice. Additionally, CD47 macrophages and preosteoclasts exhibited decreased RANKL induced proliferation as measured by BrdU incorporation. In contrast, CD47 mature OCs demonstrated decreased apoptosis at later stages of development. Phospho-p38 signaling was decreased in RANKL stimulated CD47- macrophages, whereas NFkB signaling was intact. Our data suggest that disrupted CD47 mediated signaling in macrophages leads to reduced osteoclast differentiation possibly through a RANKL dependent pathway. The decreased tumor growth seen in this model suggests that host CD47 expression can modulate tumor growth in bone. We hypothesize that CD47 could be a novel molecular target for treating bone metastasis and ismo. Generic MicronaseMicronase therapyMonster blood 4, unconscious living, chlamydia the clap, enteric juice and modified bruce protocol chart. Artificial insemination in the philippines, flood warning westchester, denture houston and hemolysis bacillus or speech therapy vocabulary. Discount DrugsMicronase information, discount generic imcronase online, generic micronase, mivronase therapy and Discount Drugs. Midronase drug interactions, micronase ingredients, order micronase and what is micronase or micronase tabs. Copyright © 2009 by Online-order.tripod.com Inc. |