The long term goal of this proposal is to elucidate the role of the immune system in the regulation of bone remodeling, under both normal and pathological conditions. Two approaches are described to investigate possible interactions between the cells of the immune system and the cells of the skeletal system as well as soluble products of these cells as potential agents and effectors of these interactions. The first approach concerns the lymphokine osteoclast activating factor (OAF). The cellular interactions leading to the secretion of this product will be further studied by the use of specific monoclonal antibodies to cell surface antigens. In parallel, purification of this lymphokine will be attempted, possibly using T-cell hybrids as a source, by conventional purification methods and also by inhibition assays, affinity chromatography and immune overlay of electrophhoretical transfers if an antibody to this protein can be raised. The second approach deals with studies in vivo on immunodeficient animals (Nudes, Motheaten, Beige) on normal animals on which specific immune defects are induced and on mutants with skeletal defects (osteopetrotic). Parallel studies will be made on bone remodeling and immune functions in these three groups of animals. Finally, immunohistochemical localization of cells of the immune system relative to bone cells will be made as well as attempts at localizing known surface antigens on bone cells. In the long run, these studies may be critical importance in the understanding of the regulation of skeletal diseases such as periodontal disease, osteopetrosis and osteoporosis and primary and metastatic bone tumors. They may also lead to an expanded concept of the role of the immune system in homeostasis.
| de Vernejoul, M C; Horowitz, M; Demignon, J et al. (1988) Bone resorption by isolated chick osteoclasts in culture is stimulated by murine spleen cell supernatant fluids (osteoclast-activating factor) and inhibited by calcitonin and prostaglandin E2. J Bone Miner Res 3:69-80 |
| Baron, R; Neff, L; Roy, C et al. (1986) Evidence for a high and specific concentration of (Na+,K+)ATPase in the plasma membrane of the osteoclast. Cell 46:311-20 |
| Baron, R; Neff, L; Tran Van, P et al. (1986) Kinetic and cytochemical identification of osteoclast precursors and their differentiation into multinucleated osteoclasts. Am J Pathol 122:363-78 |
