title: Effects of matrix metalloproteinase inhibitors on bone resorption and orthodontic tooth movement.
abstract: 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.
authors.affiliation: Department of Orthodontics, College of Dentistry, University of Florida, Box 100444, JHMHC, Gainesville, FL 32610-0444, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Holliday
authors.forename: A
authors.initials: A
authors.lastname: Vakani
authors.forename: L
authors.initials: L
authors.lastname: Archer
authors.forename: C
authors.initials: C
authors.lastname: Dolce
mesh_terms: D000577:Amides / Q000494:pharmacology; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000503:physiopathology*; D018929:Cell Culture Techniques; D003692:Delayed-Action Preparations; D006877:Hydroxamic Acids; D007211:Indoles / Q000494:pharmacology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008437:Maxilla / Q000187:drug effects*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects; D011145:Polyvinyls; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000502:physiology; D014087:Tooth Movement Techniques; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000577:Amides; D003692:Delayed-Action Preparations; D006877:Hydroxamic Acids; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D011145:Polyvinyls; D011971:Receptors, Immunologic; C112658:arginyl-glycyl-glutamic acid; C065557:N-(2-isobutyl-3-(N'-hydroxycarbonylamido)propanoyl)-O-methyltyrosinemethylamide; C016438:ethylenevinylacetate copolymer; D014443:Tyrosine; C047981:arginyl-glycyl-aspartic acid; C119203:ilomastat