Читать книгу Biological Mechanisms of Tooth Movement - Группа авторов - Страница 61

IL‐1 exists in two forms, α and β, of which IL‐1β is the form mainly involved in bone metabolism, stimulation of bone resorption, and inhibition of bone formation. IL‐1β also plays a central role in the inflammatory process. The staining of feline PDL cells for IL‐1β showed the presence of bound signal complexes in the plasma membrane, which was expected as it is known that receptors for IL‐1β are present on fibroblasts (Dinarello and Savage, 1989). The response of gingival fibroblasts to IL‐1 might represent a mechanism for amplification of gingival inflammation. Further, IL‐1β may act synergistically with TNF‐α as a powerful inducer of IL‐6. Recent studies have described positive correlations between IL‐1β gingival crevicular fluid (GCF) levels and the rate of OTM, derived from low‐level laser therapy application (Varella et al., 2018; Fernandes et al., 2019).

IL‐6, a multifunctional cytokine previously referred to as B cell stimulatory factor 2, hepatocyte stimulating factor, or interferon‐α₂, is produced by both lymphoid and nonlymphoid cells. This cytokine can apparently induce osteoclastic bone resorption through an effect on osteoclastogenesis. The levels of IL‐1β and IL‐6 were significantly higher in inflamed gingivae, when compared with non‐inflamed gingival tissues in young adults. The finding that there is an elevation in levels of IL‐1α and β, and IL‐6 in the PDL and alveolar bone (Figure 4.2) following mechanical force application was demonstrated through in vivo studies (Davidovitch et al., 1988; Alhashimi et al., 2001; Bletsa et al., 2006) and in vitro studies (Saito et al., 1991; Shimizu et al., 1994; Yamamoto et al., 2006). In a general context, IL‐1β and IL‐6 are associated with inflammatory reaction development and the subsequent osteoclastogenesis, and possibly operate in a cooperative way in order to promote tooth movement. Accordingly, the IL‐1Ra, a naturally occurring IL‐1 antagonist, was demonstrated to downregulate OTM in mice (Salla et al., 2012). As described for IL‐1, recent studies have shown positive correlations between IL‐6 GCF levels and the rate of OTM associated with photobiomodulation (Fernandes et al., 2019).

IL‐17 is an inflammatory cytokine that is produced exclusively by activated T cells (Th17 cells) (Yao et al., 1995). IL‐17 has been shown to be an important mediator of autoimmune diseases, including rheumatoid arthritis (Kotake et al., 1999), multiple sclerosis (Ishizu et al., 2005; Lock et al., 2002), and allergic airway inflammation (Molet et al., 2001). Recently, IL‐17 has been reported to induce osteoclastogenesis directly from monocytes alone (Yago et al., 2009). In addition, IL‐17 induces RANKL production by osteoblasts, and was shown to be related to bone destruction in periodontitis (Kotake et al., 1999; Johnson et al., 2004). Moreover, it has been shown that compressive force stimulates the expression of the IL‐17 genes and their receptors in MC3T3‐E1 cells, and also results in the induction of osteoclastogenesis (Zhang et al., 2010). Further, the immunoreactivity for Th17, IL‐17, IL‐17R, and IL‐6 was detected in PDL tissues subjected to orthodontic force on day 7 (Hayashi et al., 2012). Yamada et al. (2013) reported that the immunoreactivities for TRAP, IL‐17, IL‐6, and RANKL in the atopic dermatitis group were found to be significantly increased. The secretion of IL‐17, IL‐6, and RANKL, and the mRNA levels of IL‐6 and RANKL in the atopic dermatitis patients were increased compared with those in healthy individuals when subjected to orthodontic force application. These cytokines may therefore also contribute to alveolar bone remodeling during OTM.

Figure 4.2 Immunohistochemical localization of the cytokine IL‐1α in a 6 μm sagittal section of a maxillary canine from a 1‐year‐old male cat. (a) This section was obtained from a maxillary canine that had not been subjected to orthodontic force (control). A few PDL fibroblasts are stained lightly (brown) for IL‐1α. Light staining intensity is suggestive of a low cellular concentration of the cytokine. (b) This tooth was subjected to 80 g of translatory force for 6 hours. The cells in this photograph are located in the tension zone, and are stained intensely for the cytokine, indicative of high cellular concentrations, compared with the control. Many of the cells appear elongated due to stretching. The round‐shaped cells may have already detached themselves from the stretched extracellular matrix. (c) The cells in the photographs belong to the compression zone. They are stained intensely for IL‐1α. The shape of most cells is round, either because of a reduction in available space due to pressure, or because of cell detachment from the surrounding matrix.

(Source: Courtesy Dr. Ze’ev Davidovitch.)

While some cytokines have been positively associated with the inflammatory reaction and bone resorption occurring during OTMs, others have been described as presenting an inverse effect. The expression of anti‐inflammatory cytokine, IL‐10, is significantly higher on the tension side than the compression side (Garlet et al., 2007). Accordingly, it was demonstrated that tensile strain induces IL‐10 synthesis in PDL (Long et al., 2001). In this context, IL‐10 is supposed to counteract the effect of inflammatory cytokines during the tooth‐movement process and contribute to bone formation in PDL tension areas. Indeed, previous studies demonstrate an important role for IL‐10 in bone metabolism in vivo, as IL‐10‐deficient mice present an increased inflammatory responsiveness, decreased osteoblast generation and bone formation (Claudino et al., 2010). These findings suggest that both pro‐ and anti‐inflammatory interleukins play an important role in mechanical‐force‐induced OTM.