Biological Mechanisms of Tooth Movement. Группа авторов
apoptosis occurred following cell proliferation in response to mechanical stress. Mabuchi et al. (2002) reported that the ratios of cell proliferation and cell death were closely related to the regeneration and reconstruction of PDL in response to orthodontic force. Therefore, the rate of tooth movement may be involved in the ratios of cell proliferation and cell death of PDL cells. Furthermore, TNF‐α plays a significant role in the control of proliferation, differentiation, and apoptosis. TNF‐α has been shown to trigger apoptosis in osteoblast and PDL cells. Sugimori et al. (2018) concluded that micro‐osteoperforations may accelerate tooth movement through activation of cell proliferation and apoptosis of PDL cells.
These present and previous findings suggest that activation of inflammation, apoptosis, and cell cycles of PDL may potentially increase the rate of tooth movement.
Response of the dental pulp to mechanical forces
The dental pulp is a highly vascularized tissue situated in an inextensible environment surrounded by rigid dentin walls. The pulp vascular system is not only responsible for nutrient supply but also contributes actively to the pulp inflammatory response and subsequent regeneration (Rombouts et al., 2017).
Periodontal and pulpal blood flow increased by rat experimental tooth movement (Kvinnsland et al., 1989) and humans (Sabuncuoglu and Ersahan, 2015). Furthermore, the expression of HIF‐1α and VEGF was enhanced by mechanical force. HIF‐1α and VEGF may play an important role in retaining the homeostasis of dental pulp during OTM (Wei et al., 2015)
Römer et al. (2014) showed the induction of hypoxia in dental pulp after OTM. The induction of oxidative stress in human dental pulp cells showed up‐regulation of the proinflammatory and angiogenic genes Cox‐2, VEGF, IL‐6, and IL‐8. It suggests that OTM affects dental pulp circulation by hypoxia, which leads to an inflammatory response inside treated teeth.
Recent studies reported that an orthodontic force mediated the IL‐17 level in the dental pulp microenvironment (Yu et al., 2016). Therefore, pulp tissue may be expected to undergo a remodeling process after tooth movement.
Figure 4.4 Immunohistochemical staining for CGRP in cat PDL after canine retraction. (a) Control; (b) seven days after tooth movement in tension side; (c) seven days after tooth movement in compression side; (d) 28 days after tooth movement in tension side; (e) 28 hours after tooth movement in compression side.
(Source: Courtesy of Dr. Ze’ev Davidovitch.)
Neuropeptide response in dental pulp to orthodontic force
The innervation of the dental pulp includes sensory nerve fibers, which may also subserve dentinal fluid dynamics and regulate pulpal blood flow, providing reflexes to preserve dental tissues and promote wound healing. The main neuropeptides associated with these functions include SP, CGRP, and NKA, which are abundant in the pulp and periodontium (Kim, 1990; Ohkubo et al., 1993). Release of these neuropeptides after stimulation of sensory nerve fibers induces vasodilatation and increases vascular permeability, a condition referred to as neurogenic inflammation (Fristad et al., 1997). It is concluded that the stimulation of sensitive teeth may induce pulpal changes such as induction of neurogenic inflammation and alteration of pulpal blood flow.
The morphology and distribution of CGRP and SP through immunoreactive nerves have been shown to change their pattern as a result of local pulp trauma, indicating their role in the inflammatory process in connection with tissue injury and repair. The expressions of SP, CGRP, and NKA in inflamed human dental pulp tissue are significantly higher compared with healthy pulp. In addition, it was observed that the expression of CGRP and/or SP increases in the dental pulp in response to orthodontic treatment in rats, cats, and humans (Parris et al., 1989; Kvinnsland and Kvinnsland, 1990; Norevall et al., 1998). Another report suggested that these neuropeptides might be involved in inflammation of the dental pulp at the time of OTM (Norevall et al., 1995). Previous immunohistochemical studies demonstrated that MMP‐1, 3, 8, 9, and tissue‐type plasminogen activator expressions were significantly higher in the inflamed pulps than in clinically healthy pulps. These mediators may play an important role in the pathogenesis of pulpal inflammation.
Yamaguchi et al. (2004) reported that SP and CGRP stimulated the production of IL‐1β, IL‐6, and TNF‐α in human dental pulp fibroblasts (HDPF) in vitro. Moreover, Kojima et al. (2006) reported that SP significantly stimulated the production of PGE2 and RANKL by HDPF cells, and the increase of RANKL caused by SP stimulation in HDPF cells were partially mediated by PGE2. Shimizu et al. (2013) demonstrated that the immunoreactivity for Th17, IL‐17, IL‐17R, IL‐6 and KC (IL‐8 related protein in rodents) in the atopic dermatitis group was found to be increased in the dental pulp tissue subjected to the orthodontic force on day 9. The atopic dermatitis patients increased the release of IL‐6 and IL‐8 from human dental pulp cells. Taken together, these findings and our results suggest that HDPF may be actively involved in the progress of inflammation in the pulp tissue during OTM.
Vasodilatation and angiogenesis response to orthodontic forces
Blood flowing through the tooth is confronted with a unique environment. The dental pulp is encased within a rigid, noncompliant shell and its survival is dependent on the blood vessels that access the interior of the tooth through the apical foramen. As a consequence of these unusual environmental constraints, changes in pulpal blood flow or vascular tissue pressure can have serious implications for the health of the dental pulp (Kim, 1990).
The changes occurring in respiration in the dental pulp tissue while it is being subjected to orthodontic force have been reported (Hamersky et al., 1980). Kvinnsland et al. (1989) described a detectable increase in the pulpal blood flow in rats caused by an orthodontic appliance. Rana et al. (2001) found apoptosis in dental pulp tissues of rats undergoing orthodontic stress, whereas Derringer et al. (1996) observed an increase in angiogenesis in human dental pulp tissue following orthodontic force application. Further, aspartate aminotransferase, a cytoplasmic enzyme that is released extracellularly upon cell death, was elevated in the pulp of orthodontically treated teeth (Perinetti et al., 2004). The role of the vascular system and blood circulation incident to OTM has been studied by several investigators. It was concluded that orthodontic force might stimulate vasodilatation in dental pulp tissues (Yamaguchi and Kasai, 2007). The processes that occur in the dental pulp, which were explored in in vivo and in vitro studies, are summarized in Table 4.3.
Pain during OTM
OTM causes inflammatory reactions in the periodontium and dental pulp, which will stimulate release of various biochemical mediators. The perception of orthodontic pain is the result of a hyperalgesic response elicited by these mediators. Periodontal pain is caused by a process involving the development of pressure, ischemia, inflammation, and edema. Burstone (1964) identified both immediate and delayed pain responses, which begin a few hours after the application of an orthodontic force and last for approximately 5 days (Scheurer et al., 1996). Krukemeyer et al. (2009) concluded from a survey conducted on 118 patients that 58.5% indicated that they experienced pain for a few days after their appointment, out of which only 26.5% of the patients used pain medication immediately following and 1 day after the last appointment.