Bone disorders and their complications are the major cause (40 percent) of all disabilities in Americans and yield high cost in both economic and human terms. The goal of these studies is to develop and refine a novel strategy that would augment the healing and regeneration of bone mediated by grafts. Bone cells in vitro, including cells of osteoblastic lineage as well as osteoclasts, attach and spread on adhesive proteins, their fragments yielded by enzymatic digestion as well as synthetic peptides corresponding to the cell-binding domain(s) of extracellular matrix components. These interactions are mediated predominantly by integrins, a class of transmembrane receptors. Integrin-ligand interactions influence many fundamental cell processes, including migration, proliferation and differentiation. Preliminary experiments have shown that incorporation of the Arginine-Glycine- Aspartate (RGD) cell attachment motif into the bone graft enhances the process of bone induction in heterotopical sites. Therefore, we hypothesize that synthetic peptides containing the integrin-binding motif when incorporated into the devitalized bone graft will enhance the healing of bone defects as well. In order to test this hypothesis, we propose the following specific aims: 1) to establish the optimal concentration of synthetic integrin ligands in the bone grafts; 2) to test the performance of such modified grafts in an animal model of bone healing. This research may have an immediate impact on various clinical procedures where bone allografts are employed.
| Grzesik, W J; Cheng, H; Oh, J S et al. (2000) Cementum-forming cells are phenotypically distinct from bone-forming cells. J Bone Miner Res 15:52-9 |
