CMT-3 inhibits orthodontic tooth displacement in the rat

Objectiue: Orthodontic tooth movement requires extensive remodeling of the periodontal ligament (PDL) and the alveolar bone. Osteoclasts resorb bone, allowing teeth to migrate in the direction of the force. Matrix metalloproteinases (MMPs) are able to degrade the extracellular matrix of the periodontal tissues. Chemically modified tetracyclines (CMTs) can inhibit MMPs, but lack antimicrobial activity. We hypothesize that CMT-3 will decrease the rate of orthodontic tooth movement in the rat. Design: Eighteen Wistar rats received a standardized orthodontic appliance at one side of the maxilla. During 14 days, three groups of six rats received a daily dose of 0, 6 or 30 mg/kg CMT-3, and tooth displacement was measured. Thereafter, osteoclasts were counted on histological sections using an ED-1 staining. Multi- and mononuclear ED-1-positive cells in the PDL were also counted. in addition, sections were stained for MMP-9. Results: CMT-3 significantly inhibited tooth movement (p = 0.03) and also decreased the number of osteoclasts at the compression sides in the 30 mg/kg group (p < 0.05). Significantly more mono-than multinuclear ED-1-positive cells were present in the PDL, but no significant differences were found between the dosage groups. Osteoclasts in the 30 mg/kg group seemed to contain less MMP-9 than in the control. Conclusions: CMT-3 inhibits tooth movement in the rat, probably by reducing the number of osteoclasts at the compression side. This might be due to induction of apoptosis in activated osteoclasts or reduced osteoclast migration. Reduced MMP activity by CMT-3 might also directly inhibit degradation of the organic bone matrix. (C) 2006 Elsevier Ltd. All rights reserved.