CMT-3 inhibits orthodontic tooth displacement in the rat.
OBJECTIVE
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.


METHODS
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 30mg/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 30mg/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 30mg/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.
Bildt
M M
MM
Radboud University Nijmegen Medical Centre, Department of Orthodontics & Oral Biology, Philips van Leydenlaan 25, Nijmegen, Netherlands.
Henneman
S
S
Maltha
J C
JC
Kuijpers-Jagtman
A M
AM
Von den Hoff
J W
JW
D000539:Alveolar Process / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D002452:Cell Count; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D009967:Orthodontic Appliances; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010513:Periodontal Ligament / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013754:Tetracyclines / Q000494:pharmacology*; D014087:Tooth Movement Techniques / Q000295:instrumentation; D014092:Tooth Root / Q000187:drug effects / Q000473:pathology
D061965:Matrix Metalloproteinase Inhibitors; D008562:Membrane Glycoproteins; D013754:Tetracyclines; C117155:tetracycline CMT-3; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9