1. Introduction

Orthodontic tooth movement is a biological process that requires the relay of mechanical loading to biological signals by periodontal ligament (PDL) and alveolar bone (AB) cells such as osteoblasts, osteocytes and osteoclasts. The mechanotransduction of signals involves dynamic cellular communication which allows for coordinated cellular response of alveolar bone remodeling and periodontal tissue homeostasis that occurs in response to orthodontic force. This complex process depends on adaptive tissue remodeling of periodontium for both anabolic and catabolic events. Compression and tension forces from orthodontic treatment create stress and strain to the PDL and AB cells and their surrounding extracellular matrices (ECM), which respond to the stress and strain from orthodontic forces by expressing and secreting

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and eproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

biologic mediators and inflammatory cytokines, osteoclast differentiation factors and ECM proteins such as collagen I, III, V and their modifying enzymes and proteases. These biomolecules, in turn, initiate the activation of fibroblasts, osteoblasts, osteocytes and recruitment and differentiation of osteoclasts leading to anabolic activities on the tension side and increased osteoclastic activity and low bone density on the compression side of tooth movement. These cellular and molecular events are strictly controlled at transcriptional, posttranscriptional and translational levels and the interference of these events affects the rate of tooth movement. Therefore, understanding the mechanism of cellular and molecular events of tooth movement will allow us to apply the cutting edge knowledge to improve clinical orthodontic practice using gene therapy or molecular biology approaches.

afferent nerve endings [11]. A report showed that the nerve ending released the neuropeptides

Advances in Orthodontic Tooth Movement: Gene Therapy and Molecular Biology Aspect

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4. Fluid flow shear stress model: it was based on the concept that osteocytes respond to mechanical forces. Locally strain derived from the displacement of fluid in bony canaliculi of osteocytes is very important [13]. When loading occurs, interstitial fluid squeezes through the thin layer of the non-mineralized matrix surrounding the cell bodies and cell processes, resulting in local strain at the cell membrane and activation of the affected osteocytes [14]. With regard to orthodontic force, the force on the side of the tooth receiving orthodontic pressure creates shear stress and activates responses on osteocytes [15]. The shear stress on the osteocytes induces increased secretion of biological mediators from the osteocytes leading to activation of osteoclasts [16, 17]. At the same time, on the tension side, the increased pulling force on the periodontal ligament is transferred to the bone. The resulting deformation drives the fluid flow shear stress on the network of osteocytes. This shear stress induces osteocyte activation, and osteocytes respond by secreting signaling

In addition, it has been shown that compressive force induces bone matrix deformation and microcracks; and the accumulation of microscopic cracks in the bone matrix may induce additional damage to osteocytes in the microcrack region [18]. Microcracks are more prevalent on the pressure-side than on the tension-side of the tooth, and it has been hypothesized that microcracks were the first damage induced by the orthodontic force to induce osteocyte apoptosis and bone remodeling. Osteocyte apoptosis has been observed at the pressure side in an experimental tooth movement model in animal models, which may be associated with the subsequent bone resorption [19, 20]. Therefore, the microcracks may play a role in the initiation of bone resorption on the pressure side of the tooth under the compressive force of

Although there are several models proposed to explain the events of orthodontic tooth movement, no single model could directly and comprehensively explain this process. The evidence from histological and animal studies has shown that this complex biological process is initiated from the application of mechanical forces onto the orthodontic appliances, which converts into the biological signals to stimulate mechanosensitive cells. (Figure 1) [22] Literatures showed that orthodontic force application induced physiologic adaptation of alveolar bone with small magnitude of reversible injury to periodontium [23]. Significant evidence suggests that when mechanical loading forces are relayed from the orthodontic appliances to the PDL and bone tissues, the mechanoreceptor cells percept the loading forces as shear stress and strain [24] as the tooth shifts its position in the PDL space resulting in compression and tension areas in PDL

The sequence of biological events after loading of orthodontic force occurs as (1) fluid flow changes and matrix strain (Figure 2); (2) strain on mechanoreceptor cells (Figure 2); (3) cell activation (Figure 3); and (4) tissue remodeling leading to tooth movement (Figure 4) [15].

after periodontal ligament had been strained by the force applied to the tooth [12].

molecules that contribute to osteoclast recruitment and differentiation.

3. Molecular mechanism of orthodontic tooth movement

orthodontic loading [21].

and bone tissues [25].
