Orthodontic tooth movement and neurotrophins in the rat dento-alveolar complex.

Abstract

During orthodontic tooth movement, stress is applied on the dento-alveolar complex, initiating a biological response. This response results in the remodelling of the periodontal ligament and the alveolar bone. When a force is placed on a tooth, the periodontal ligament is stretched and compressed depending on the direction of force. On the side where the ligament is stretched, a response resulting in bone deposition is initiated. On the opposite side, where the periodontal ligament is compressed, a response resulting in the resorption of bone begins. These responses are believed to be modulated by factors that are derived from the immune or nervous systems. When stress is placed on the periodontal ligament, it is believed that nerve fibres and neuroreceptors within the tissue are distorted, leading to the release of neurotrophins and a common concomitant clinical response of pain and pressure. These neurotrophins may interact with cells within the dentoalveolar complex, including fibroblasts, endothelial and alveolar bone cells, resulting in the initiation of bone resorption via the activation of intracellular secondary messengers, which leads to cellular proliferation and differentiation. Neurotrophin levels may play a role in the modulation of cellular activity in the periodontal ligament during orthodontic movement. They are a family of protein polypeptides which are important in neural cell differentiation and survival. One relatively well studied member of the family, Nerve Growth Factor (NGF), is a polypeptide essential for supporting cholinergic innervation in the brain and sympathetic and sensory innervation in the peripheral tissues. Within the dento-alveolar complex, the function and localization of neurotrophins and their receptors are yet to be determined. Previous studies have shown that there is an increase in NGF expression in tissues in response to injury, suggesting that NGF expression may increase in regions within the dento-alveolar complex where inflammation and bone remodelling are occurring. A study showed elevated levels of NGF mRNA in human periodontal ligament cells in vitro during increased transcription and translation of the bone-related proteins alkaline phosphatase and osteopontin, suggesting NGF facilitates bone formation. The NGF may be modulating cellular activity within the periodontal ligament. O’Hara et al. used immunohistochemical staining in the rat dento-alveolar complex to show that there was evidence of an increase in NGF synthesis and release by certain cells or tissues within the region of alveolar bone remodelling during the initial injury response period to orthodontic tooth movement. Ho used a similar model to test the hypothesis that there may be a positive relationship between the presence of osteoclasts and pre-osteoclasts with areas of NGF localisation. He found no relationship between osteoclasts and areas of NGF; however, his findings showed areas of unknown tissue within the periodontal ligament that were associated with NGF. To date, the relationship between NGF and the cellular process of orthodontic tooth movement remains unknown. Further studies are required to describe the distribution of neurotrophins and neurotrophic receptors and cellular interactions within the rat dento-alveolar complex.