Effects of matrix metalloproteinase inhibitors on bone resorption and orthodontic tooth movement.
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.
Holliday
L S
LS
Department of Orthodontics, College of Dentistry, University of Florida, Box 100444, JHMHC, Gainesville, FL 32610-0444, USA.
Vakani
A
A
Archer
L
L
Dolce
C
C
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
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