**Note**

of bone remodeling, after a mechanical stress, β<sup>2</sup>

the increased periodontal remodeling caused by these forces [20].

application of cytokine, the results could be very useful.

formation [49].

44 Current Approaches in Orthodontics

bone metabolism, with the function of a stimulator of the osteoclast activity in the resorption stage and the function of the increase of the binding for bone cells *IGF-I* in the stage of bone

Apart from pro-inflammatory cytokines and other pro-inflammatory substances, during the orthodontic tooth movement to gingival fluid, various metabolites are released, too. For lactate-dehydrogenase (*LDH*) [21] and metalloproteinase 8 [20], it is shown that they increase their level or the activity simultaneously with pro-inflammatory cytokines, in approximately the same time, so it is considered that their existence reflects the increased periodontal remodeling caused by orthodontic forces primarily at early stages of this process. *LDH* is intracellular, cytoplasmic enzyme, which is released outside the cell under conditions of cellular necrosis or tissue degradation. It is believed that the increase of the *LDH* level at gingival fluid during the orthodontic tooth movement follows the process of bone resorption [21]; metalloproteinase 8 is the isoform of the enzyme of collagenase, which is released from periodontal fibroblasts due to the effects of mechanical forces. In the increased level in gingival fluid, it emerges during the initial stage of the orthodontic tooth movement, expressing

The damage of dental tissues caused by inflammation and its reparation are based on many elements and their coordination inside and outside cells. Even though there are differences between pathological inflammatory changes and those which accompany mechanically caused reshaping of tissues, the basic cellular responses to stimuli, regardless of their nature, express essentially the same properties [50]. Our researches of changes of individual integral parts of the immune system and ECM in normal and inflammatory gingiva [51–53] were the basis for the examination of the expression of IL*-1β, IL-6*, and *TNF-α* and their mutual relation in gingival fluid and tissue of gingiva of children and adults who underwent the orthodontic treatment. Analyzing the causes of gingival fluid and tissue of free gingiva of orthodontically treated teeth (experimental teeth) and their nontreated antagonists (control teeth) in four different moments in time ("zero" hour, 24th hour, 72nd hour, and 168th hour after the application of the separator), we have reached the knowledge about the dynamics of the change in the local cytokine network during the initial stage of orthodontic tooth movement and differences existing in the amplitude of these changes between children and adult examinees [54]. The results led us to assume that in the first moments of orthodontic treatment, the constitutive creation of pro-inflammatory cytokines is created and then it is overcome in the following time intervals by more expressive reaction of cells to the effects of mechanical force. The time coincidence of quantitative changes of *IL-1β, IL-6*, and *TNF-α* in gingival fluid and tissue expression of orthodontically treated teeth indicate that these three cytokines could be in specific interdependence during the early stage of the orthodontic tooth movement. Put into the context of the concept about the pharmacological modulation of the tooth movement, especially the aspect which leads the acceleration of the process of tooth movement in the connection with the local


The execution of this chapter was financially supported by the Ministry for Science and Technological Development of the Republic of Serbia (project no. OI175061).
