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.

We tested whether orthodontic tooth movement (OTM) could be blocked by local administration of echistatin or an arginine-glycine-aspartic acid (RGD) peptide, agents known to perturb bone remodeling, adjacent to maxillary molars in rats. These molecules were incorporated into ethylene-vinyl acetate (ELVAX), a non-biodegradable, sustained-release polymer. In vitro experiments showed that the echistatin and RGD peptide were released from ELVAX in active forms at levels sufficient to disrupt osteoclasts. Biotinylated RGD peptide was released from ELVAX into the PDL after surgical implantation. ELVAX loaded with either RGD peptide or echistatin and surgically implanted next to the maxillary molars inhibited orthodontic tooth movement (p < 0.01). The RGD peptide also reduced molar drift (p < 0.05). This study shows the feasibility of using ELVAX to deliver integrin inhibitors adjacent to teeth to limit local tooth movement in response to orthodontic forces.