The steps leading from the application of orthodontic forces to a tooth and the remodeling events that accompany tooth movement are not well understood. Orthodontic tooth movement (OTM) involves two processes - bone deposition by osteoblasts that become activated on the tension side of the socket and bone resorption by osteoclasts on the pressure side. The kinetics of tooth movement after application of orthodontic forces can be divided into three phases: an initial tipping phase where cells are activated; a lag phase when osteoclasts are recruited to the site and begin to resorb bone and finally, the post-lag phase when tooth movement occurs. The complex cell-matrix interactions that occur in the microenvironment of the tooth socket during OTM involve a family of adhesion molecules called integrins. These molecules have been shown to play a role in periodontal homeostasis and disease progression. Importantly, blocking of the integrin receptor with compounds like echistatin, inhibits osteoclast attachment to bone and consequently inhibits bone resorption. These studies will use a rat model of experimentally-induced OTM to test the fundamental hypothesis that signal detection by integrin receptors is essential to maintain adequate numbers and activity of osteoblasts and osteoclasts for increased alveolar bone turnover to occur during orthodontic tooth movement.
Aim 1 experiments will examine the kinetics of OTM in this model following the use of a synthetic RGD peptide.
Aim 2 experiments will assess the rate and extent of alveolar bone turnover using histomorphometric means. These data may demonstrate the usefulness of the RGD peptide in modulating both bone formation and resorption during OTM.
| Zuo, J; Archer, L A; Cooper, A et al. (2007) Nuclear factor kappaB p65 phosphorylation in orthodontic tooth movement. J Dent Res 86:556-9 |
| Holliday, L S; Vakani, A; Archer, L et al. (2003) Effects of matrix metalloproteinase inhibitors on bone resorption and orthodontic tooth movement. J Dent Res 82:687-91 |
| Dolce, C; Vakani, A; Archer, L et al. (2003) Effects of echistatin and an RGD peptide on orthodontic tooth movement. J Dent Res 82:682-6 |
