intensities revealed that paradental cells are very sensitive to the application of orthodontic forces, that this cellular response begins as soon as the tissues develop strain, and that these reactions encompass cells of the dental pulp, PDL, and alveolar bone marrow cavities. Figure 1.16 shows a cat maxillary canine section, stained immunohistochemically for prostaglandin E2 (PGE2), a 20‐carbon essential fatty acid, produced by many cell types and acting as a paracrine and autocrine. This canine was not treated orthodontically (control). The PDL and alveolar bone surface cells are stained lightly for PGE2. In contrast, 24 hours after the application of force to the other maxillary canine, the stretched cells (Figure 1.17) stain intensely for PGE2. The staining intensity is indicative of the cellular concentration of the antigen in question. In the case of PGE2, it is evident that orthodontic force stimulates the target cells to produce higher levels than usual of PGE2. Likewise, these forces increase significantly the cellular concentrations of cyclic AMP, an intracellular second messenger (Figures ), and of the cytokine interleukin‐1β (IL‐1β), an inflammatory mediator, and a potent stimulator of bone resorption (Figures 1.21 and 1.22).
Figure 1.16 A 6 μm sagittal section of a cat maxilla, unfixed and nondemineralized, stained immunohistochemically for PGE2. This section shows the PDL‐alveolar bone interface near one canine that received no orthodontic force (control). PDL and alveolar bone surface cells are stained lightly for PGE2.
The era of cellular and molecular biology as major determinants of orthodontic treatment
A review of bone cell biology as related to OTM identified the osteoblasts as the cells that control both the resorptive and formative phases of the remodeling cycle (Sandy et al. 1993). A decade after this publication, Pavlin et al. (2001) and Gluhak‐Heinrich et al. (2003) highlighted the importance of osteocytes in the bone remodeling process. They showed that the expression of dentine matrix protein‐1 mRNA in osteocytes of the alveolar bone increased twofold as early as 6 hours after loading, at both sites of formation and resorption. Receptor studies have proven that these cells are targets for resorptive agents in bone, as well as for mechanical loads. Their response is reflected in fluctuations of prostaglandins, cyclic nucleotides, and inositol phosphates. It was, therefore, postulated that mechanically induced changes in cell shape produce a range of effects, mediated by adhesion molecules (integrins) and the cytoskeleton. In this fashion, mechanical forces can reach the cell nucleus directly, circumventing the dependence on enzymatic cascades in the cell membrane and the cytoplasm.
Figure 1.17 A 6 μm sagittal section of the same maxilla shown in Figure 1.16, but derived from the other canine that had been tipped distally for 24 hours by a coil spring generating 80 g of force. The PDL and alveolar bone‐surface cell in the site of PDL tension are stained intensely for PGE2.
Figure 1.18 Immunohistochemical staining for cyclic AMP in a 6 μm sagittal section of a cat maxillary canine untreated by orthodontic forces (control). The PDL and alveolar bone surface cells stain mildly for this cyclic nucleotide.
Figure 1.19 Staining for cyclic AMP in a 6 μm sagittal section of a cat maxillary canine subjected for 24 hours to a distalizing force of 80 g. This section, which shows the PDL tension zone, was obtained from the antimere of the control tooth shown in Figure 1.18. The PDL and bone surface cells are stained intensely for cyclic AMP, particularly the nucleoli.
Figure 1.20 Staining for cyclic AMP in the tension zone of the PDL after 7 days of treatment. The active osteoblasts are predominantly round, while the adjacent PDL cells are elongated. All cells are intensely stained for cAMP.
Figure 1.21 Immunohistochemical staining for IL‐1β in PDL and alveolar bone cells near a cat maxillary canine untreated by orthodontic forces (control). The PDL and alveolar bone surface cells are stained lightly for IL‐1β.
Figure 1.22 Staining for IL‐1β in PDL and alveolar bone surface cells after 1 hour of compression resulting from the application of an 80 g distalizing force to the antimere of the tooth shown in Figure 1.21. The cells stain intensely for IL‐1β in the PDL compression zone, and some have a round shape, perhaps signifying detachment from the extracellular matrix. × 840.
Efforts to identify specific molecules involved in tissue remodeling during OTM have unveiled numerous components of the cell nucleus, cytoplasm, and plasma membrane that seem to affect stimulus‐cell interactions. These interactions, as well as those between adjacent cells, seem to determine the nature and the extent of the cellular response to applied
