ROLE OF CALCITONIN GENE RELATED PEPTIDE IN ALLOGRAFTS

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Mounting evidence from the literature indicates that the immune system and bone cells closely interact both directly and indirectly via cytokines and soluble factors. Most recently, we have generated evidence that some immune cells express functional receptors for the neuropeptide calcitonin gene related peptide (CGRP). We have shown that CGRP in a potent immunosuppressive peptide by virtue of inhibiting T lymphocytes to produce interleukin 2 as well as cytokines which promote osteoclast differentiation and activation. Since CGRP directly inhibits osteoclast activity via calcitonin receptors, and stimulates osteogenesis in vitro, we hypothesize that CGRP plays a central role in bone homeostasis and is a potential candidate to optimize the acceptance of bone allografts. The specific aims of this proposal are: 1. To define the distribution of CGRP positive nerve endings in bone and bone marrow in vivo by immunolocalization; compare it to that observed during bone growth and repair, as well as in bone transplant and implant model systems. 2. To investigate the immunosuppressive role of CGRP in vivo using allografts. The long term goal of this research is to develop new therapies that have the potential to improve the survival of transplanted calcified tissues.