Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE010676-02
Application #
2131568
Study Section
NIDCR Special Grants Review Committee (DSR)
Project Start
1993-03-01
Project End
1995-02-28
Budget Start
1994-03-01
Budget End
1995-02-28
Support Year
2
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Orthopedics
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520