DESCRIPTION (provided by applicant): Root resorption, either physiological or pathological, results in the destruction of mineralized and non-mineralized tissues of the dental roots. Pathological root resorption, internal or external, can result from the presence of cysts, tumors, trauma, infections, periodontal disease or orthodontic treatment. This process could advance in time destroying the roots and resulting in tooth loss. Apical root resorption is one of the most common problems that orthodontists face during their practice. This process could compromise the benefits of otherwise a successful orthodontic treatment and could result in severe medico-legal ramifications. Although many clinical and histological studies have been carried out in order to elucidate the etiology and pathogenesis of external root resorption, the molecular events leading to root resorption induced by orthodontic treatment are still unknown. Currently, the only available diagnosis for root resorption is by X-rays and by the time the X-ray might detect the resorption, the process is very difficult, if not impossible, to stop. Our laboratory has established a reproducible rat animal model for tooth movement resulting in tooth resorption. In the present R21 application, we request funds to create an animal model for tooth movement without root resorption, that will allow us to differentiate between genes expressed to maintain the balance between bone resorption/apposition required to move teeth, and those expressed as consequence of disruption of this balance resulting in pathological root resorption. This will be accomplished by determining the genes expressed as result of the application of orthodontic forces resulting in either tooth movement or root resorption using DNA microarrays. We will then confirm the data obtained above using RT-PCR and we will elucidate the spatial and temporal expression of candidate genes for root resorption. A better comprehension of the molecular events associated with this pathological process in the rat animal model might provide us with the starting point for future studies in humans to facilitate the treatment, prevention and possible early diagnosis of patients at risk of developing root resorption due to orthodontic treatment.