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.

Local delivery of osteoprotegerin inhibits mechanically mediated bone modeling in orthodontic tooth movement

“…As it is not the result of tissue remodeling, the amount of movement in this phase is dependent on its biophysical limitations. During the remaining phases (days [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], the high OPG group demonstrated almost no additional molar movement.…”

“…Bisphosphonates [15,19], nitric oxide synthase inhibitor [17], echistatin [16], and matrix metallo-proteinase inhibitors [18] have all been shown to decrease tooth movement. Bisphosphonates are not indicated for orthodontic use currently, and osteonecrosis of the jaw has recently become a concern with bisphosphonate therapy [43,44].…”

“…Finally, local OPG gene transfer to sites significantly diminishes while RANKL gene transfer significantly enhances orthodontic tooth movement possibly by respectively inhibiting or enhancing RANKL-mediated osteoclastogenesis [13,14]. Orthodontic tooth movement is a well-utilized in vivo model for determining the contributions of various exogenous and endogenous agents to mechanically mediated bone modeling [15][16][17][18][19]. It results from the application of forces to teeth that cause bone resorption under pressure and bone deposition under tension.…”

The Role of Host‐derived Dentinal Matrix Metalloproteinases in Reducing Dentin Bonding of Resin Adhesives

“…Several newly developed agents, for example, Marimastat (Wojtowicz-Praga et al, 1997) and CT 1166(Fanchon et al, 2004, provide effective inhibition of MMPs. Another potent anti-MMP, Ilomastat (also called galardin) was shown to inhibit ortho-dontic tooth movement in rats (Holiday et al, 2003).…”

Levels of gingival crevicular fluid matrix metalloproteinases in periodontally compromised teeth under orthodontic forces

“…14 Orthodontic tooth movement can be delayed or prevented in mice and rats by the use of MMP inhibitors. 15,16 A few human studies [17][18][19] have quantified the presence of MMPs in GCF during orthodontic tooth movement and have reported alterations in their levels during the application of orthodontic forces. Further, total collagenase activity in the GCF of orthodontic patients treated with fixed appliances has been shown to be 10-fold that of control GCF.…”