arginyl-glycyl-glutamic-acid and ilomastat

Matrix metalloproteinases are involved in the regulation of bone remodeling. The hypothesis that matrix metalloproteinase inhibitors may be useful for experimentally limiting orthodontic tooth movement, a process involving perturbations of normal bone remodeling, was tested. General matrix metalloproteinase inhibitors limited the resorption of bone slices by mouse marrow cultures stimulated by calcitriol, parathyroid hormone, and basic-fibroblast growth factor. Pre-coating dentin slices with short arginine-glycine aspartic acid (RGD) peptides, but not arginine-glycine-glutamic acid (RGE) controls, restored bone resorption in the presence of matrix metalloproteinase inhibitors. Orthodontic tooth movement was inhibited by local delivery of Ilomastat, a general matrix metalloproteinase inhibitor, with the use of ethylene-vinyl-acetate (ELVAX) 40, a non-biodegradable, non-inflammatory sustained-release polymer. This study shows that orthodontic tooth movement can be inhibited with the use of matrix metalloproteinase inhibitors, and suggests a mechanistic link between matrix metalloproteinase activity and the production of RGD peptides.

Topics: Amides; Amino Acid Sequence; Analysis of Variance; Animals; Bone Marrow Cells; Bone Remodeling; Bone Resorption; Cell Culture Techniques; Delayed-Action Preparations; Hydroxamic Acids; Indoles; Male; Matrix Metalloproteinase Inhibitors; Maxilla; Mice; Oligopeptides; Osteoclasts; Polyvinyls; Rats; Rats, Sprague-Dawley; Receptors, Immunologic; Tooth Movement Techniques; Tyrosine