Osteoclast polarization and orthodontic tooth movement.
BACKGROUND
Osteoclasts polarize when they contact activation signals that are associated with bone. Polarization is required for bone resorption and involves highly specialized mechanisms that represent attractive targets for the development of osteoclast-specific therapeutic agents. One potential use of such agents is to block tooth movement in spatially discrete locations to provide orthodontic anchorage.


METHODS
Our group's research was directed toward the development of agents that inhibited the polarization of osteoclasts, and efforts were underway to develop means to experimentally modulate orthodontic tooth movement. We performed 'proof-in-principle' experiments demonstrating pharmacological blockades of orthodontic tooth movement using integrin and matrix metalloproteinase inhibitors in a rat model.


RESULTS
We identified novel mechanisms underlying osteoclast bone resorption. Interactions between vacuolar H(+)-ATPase and the microfilament cytoskeleton that were unique to osteoclasts were described and characterized. Our group is now seeking to make use of this new knowledge, coupled with an emerging technique, supercomputer-based molecular modeling for the rational development of novel, osteoclast-specific therapeutic agents.


CONCLUSIONS
Fresh insight into the molecular details of osteoclastic bone resorption provides new opportunities for identifying agents to selectively modulate osteoclast activity. Such agents may contribute to evolution of the practice of orthodontics.
Department of Orthodontics, University of Florida College of Dentistry, Gainesville, Florida 32610, USA. SHOLLIDAY@dental.ufl.edu
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Holliday
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Ostrov
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Wronski
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Dolce
D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000502:physiology; D000818:Animals; D001862:Bone Resorption / Q000503:physiopathology / Q000517:prevention & control; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D016023:Integrins / Q000037:antagonists & inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D023421:Models, Animal; D008958:Models, Molecular; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D051304:Profilins / Q000502:physiology; D006180:Proton-Translocating ATPases / Q000502:physiology; D051381:Rats; D014087:Tooth Movement Techniques; D014617:Vacuoles / Q000201:enzymology
D000199:Actins; D016023:Integrins; D061965:Matrix Metalloproteinase Inhibitors; D051304:Profilins; D006180:Proton-Translocating ATPases