Biological Mechanisms of Tooth Movement. Группа авторов
reported that RANK and OPG regulated the root resorption process. Yamaguchi et al. (2006) reported that the compressed PDL cells obtained from patients with severe EARR produce a large amount of RANKL and up‐regulate osteoclastogenesis. It was recently demonstrated that IL‐1β and compressive forces lead to a significant induction of RANKL‐expression in cementoblasts, suggesting that the activation of this specific cell type could direct the resorptive response to the apex area (Diercke et al., 2012). Furthermore, exposure to excessive orthodontic force by the PDL of rats produced IL‐6, IL‐8, IL‐17 in resorbed root, and these cytokines may be associated with the deterioration of root resorption (Asano et al., 2011; Hayashi et al., 2012; Yamada et al., 2013).
There have been some reports that systemic forms of chronic inflammation may exacerbate the inflammatory response during OTM, and thus predispose the teeth to increased root resorption. McNab et al. (1999) found that asthmatic patients, both well controlled with medication as well as nonmedicated individuals, have an increased incidence of orthodontically induced EARR in their maxillary molars. This observation was supported by other researchers (Owman‐Moll and Kurol, 2000), and it is also supported by the comorbidity concept, which states that a pre‐existing inflammatory condition may modify the response to a subsequent stimulus. In this context, the response to the secondary stimulus is clearly exacerbated, and can result in the development of a pathological reaction, which would not take place without the primed inflammatory status (Trombone et al., 2010; Queiroz‐Junior et al., 2011; Claudino et al., 2012). Translating such a concept to the OTM scenario, if such chronic inflammation does indeed exacerbate the underlying inflammation in OTM, then, logically, elimination of the chronic inflammation should reduce the increased incidence of root resorption. Accordingly, it has been reported that prednisolone treatment (as used in the treatment and prevention of asthma) leads to significantly less root resorption during OTM (Ong et al., 2000).
Root resorption is believed to be related initially to the force magnitude, and light forces have long been recommended for minimizing this adverse outcome. However, recent reports indicate that force magnitude may not be the most decisive etiologic factor responsible for root resorption, and that the severity of this condition is highly related to the regimen of force application. In this regard, intermittent forces cause less severe root resorption than continuously applied forces (Acar et al., 1999; Maltha et al., 2004).
A search for risk factors affiliated with the development of EARR during orthodontic treatment has led to the suggestion that individual susceptibility, genetics, and systemic factors may be significant modulators of this process. Current research on orthodontic root resorption is directed toward identifying genes involved in the process, their chromosome loci, and their possible clinical significance. Al‐Qawasmi et al. (2003) firstly reported evidences of linkage disequilibrium of IL‐1β polymorphism in allele 1 and EARR. Subsequently, other groups replicated the possible association of IL‐1β genetic variants with the root‐resorption process (Bastos Lages et al., 2009; Urban and Mincik, 2010; Iglesias‐Linares et al., 2012), and also suggested the involvement of polymorphisms in other genes, such as the vitamin D receptor (Fontana et al., 2012). Experimental data from inbred mouse strains reinforce the hypothesis that the genetic background presents a significant impact in experimentally induced root resorption (Al‐Qawasmi et al., 2006). Recent studies reported the extent of genetic influence in the root resorption process in humans. In their review on cellular and molecular pathways in the external root resorption process. Iglesias‐Linares and Hartsfield (2017) described clast cell adhesion and the specific role of α/β integrin, osteopontin, and related extracellular matrix proteins, as well as clast cell fusion and activation by the RANKL/OPG and ATP‐P2RX7‐IL‐1 pathway. On the other hand, the meta‐analysis by Nowrin et al. (2018) showed that the IL‐1β polymorphism is not associated with a predisposition to external apical root resorption. Further research is needed about the extent of genetic influence in the root resorption process.
From the above, root resorption may be regulated by genetic factors and inflammatory cytokines. The role of cytokines as well as neuropeptides, released in response to orthodontic force application, in producing root resorption is outlined in Figure 4.5.
Root resorption in the cementum
Cementum contains 65% inorganic material and 12% water on a wet‐weight basis. By volume, inorganic material comprises approximately 45%, organic material 33%, and water 22%. Cementum is less densely mineralized than dentine and enamel, contains no blood vessels, and does not undergo physiological remodelling (Selving et al., 1962; Neiders et al., 1972; Cohen et al., 1992). The chemical composition of cementum may vary by individual, and morphologically, cementum is classified as both cellular and acellular (Foster, 2017).
Chutimanutskul et al. (2005) examined the physical properties of the cementum on the buccal and lingual surfaces of the roots at the cervical third, middle third, and apical third. The authors reported a decreasing gradient in the hardness and elastic modulus of cementum in both surface groups, from the cervical to apical thirds. Apical cementum is predominately cellular, less densely mineralized, and has lower hardness and elastic modulus values than the more densely mineralized acellular cementum found in the middle and cervical thirds of the root (Foster, 2017) . Therefore, the hardness and elastic modulus of cementum depend on the direction of the structural arrangement and the mineral content of the cementum (Henry and Weinmann, 1951; Jones and Boyde, 1972; Rex et al., 2005). Several studies have reported that the hardness of mineralized tissues was positively correlated with the extent of mineralization (Brear et al., 1990; Mahoney et al., 2000; Malek et al., 2001). Some have suggested that the mineral content of cementum might influence the resistance or susceptibility to root resorption.
Yamaguchi et al. (2016) examined whether there was individual variation in the Vickers hardness value of the cementum at the surface of the crown and root at three locations (cervical third, middle third, and apical third) of human first premolar teeth. The results of the study demonstrated that the hardness of the cementum decreased from the cervical to apical regions of the root surfaces. Furthermore, individual variations were observed in the hardness of the cementum, and the Vickers hardness value of the hard group was approximately two times higher than that of the soft group.
Yao‐Umezawa et al. (2017) investigated whether individual variation in the hardness and chemical composition of the root apex of the cementum affects the degree of root resorption. In a pit formation assay, the resorbed area in the soft group showed a greater increase than the moderate and hard groups. A correlation was noted between the Vickers hardness and the resorbed area of the cementum in the apical cementum. The Ca/P ratio of the cementum in the soft and moderate groups showed greater decreases than the hard group. A correlation was noted between the Vickers hardness and the Ca/P ratio of the cementum in the apical cementum. These results suggested that the hardness and Ca/P ratio of the cementum may be factors in the occurrence of root resorption caused by orthodontic forces. Furthermore, Iglesias‐Linares and Hartsfield (2017) suggested regulatory mechanisms of root resorption repair by cementum at the proteomic and transcriptomic levels.
Conclusions
Tooth movement by orthodontic force application is characterized by remodeling changes in dental and paradental tissues, including the dental pulp, PDL, alveolar bone, and gingiva. Studies during the early years of the twentieth century attempted mainly to analyze the histological changes in paradental tissues during and after tooth movement. Those studies have demonstrated that OTM causes inflammatory reactions in the periodontium and dental pulp. These reactions stimulate the release of various biochemical signals and mediators, causing alveolar bone remodeling and pain.
Although the orthodontic patient may feel periodic discomfort during treatment, the inflammation occurring along the entire duration of treatment is a crucial phenomenon because it is stationed in the heart of the remodeling process that facilitates tooth movement. Therefore, the control of inflammation and the efficiency of OTM are closely intertwined. Continuous unfolding