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CHAPTER 4 Inflammatory Response in the Periodontal Ligament and Dental Pulp During Orthodontic Tooth Movement
Masaru Yamaguchi and Gustavo Pompermaier Garlet
Summary
Orthodontic tooth movement is induced by mechanical stimuli and facilitated by remodeling of the periodontal ligament and alveolar bone. A precondition for these remodeling activities, and ultimately for tooth displacement, is the occurrence of an inflammatory process in the periodontium and dental pulp, in response to the mechanical damage caused by orthodontic forces. Recent data suggests that cellular/tissue stress or damage‐related products, such as damage‐associated molecular pattern molecules, can trigger an aseptic inflammatory response. Vascular and cellular changes were the first events to be recognized and described, and a number of inflammatory mediators of immune and neural origin, such as cytokines, growth factors, and neuropeptides have been demonstrated in the periodontal supporting tissues. Their increased levels during orthodontic tooth movement have led to the assumption that a network of interactions between cells producing these substances (i.e., nerve, immune, and endocrine system cells), regulate the biological responses that occur following the application of orthodontic forces. Peripheral nerve fibers and neurotransmitters are also involved in the inflammatory process and bone remodeling as evidenced by the presence of neurogenic inflammation‐related substances such as calcitonin gene regulated peptide and substance P, leading to increased vasodilation, increased microvasculature permeability, production of exudate, and increased proliferation of endothelial cells and fibroblasts. Inflammatory mediators of immunological origin, such as prostaglandins, interleukins (ILs; IL‐1, IL‐6, IL‐17) as well as cytokines of the tumor necrosis factor α superfamily, which includes the RANK/RANKL/osteoprotegerin system, are also described in the periodontal ligament and dental pulp in increased levels after orthodontic force application. Considering the importance of RANK, RANKL, and osteoprotegerin in physiological osteoclast formation, it is reasonable to propose that the RANKL/RANK/osteoprotegerin system plays an important role in orthodontic tooth movement. This chapter reviews current knowledge regarding the role of inflammation in the periodontal tissue reactions in response to orthodontic forces.
Introduction
Orthodontic tooth movement (OTM) is induced by mechanical stimuli and facilitated by remodeling of the periodontal ligament (PDL) and alveolar bone. A precondition for these remodeling activities, and ultimately for tooth displacement, is the occurrence of an aseptic inflammatory process. Vascular and cellular changes were the first events to be recognized and described, and a number of inflammatory mediators, including cytokines and neuropeptides, have been demonstrated in periodontal supporting tissues. Their increased levels during OTM have led to the assumption that interactions between cells producing these substances, such as nerve, immune, and endocrine system cells, regulate the biological responses that occur following the application of orthodontic forces (Krishnan and Davidovitch, 2006a).
Mechanical stress evokes biochemical responses and structural changes in a variety of cell types in vivo and in vitro. The overall objective of many investigations has been to further the understanding of the mechanisms involved in converting molecular and/or mechanical stress to the cellular responses that result in tooth movement. The recent advances in the understanding of the mechanisms underlying so‐called aseptic inflammation, mediated by tissue damage products collectively denominated damage associated molecular pattern proteins (DAMPs), have provided a rationale for inflammatory response triggering after orthodontic force‐induced mechanical stress/damage (Chen and Nunez, 2010). In sites at which inflammation and tissue destruction have occurred, cells may communicate with one another through the interaction of cytokines and other related molecules. Thus it is important to elucidate completely the complex cytokine cascade flow associated with inflammation‐mediated tissue destruction at the molecular level (Davidovitch et al., 1988), as well as the intricate molecular network where the simultaneous action and presence of several mediators can determine the outcome of the response to the orthodontic force. This chapter reviews current evidence regarding the role of inflammation in the periodontal tissue reactions in response to orthodontic force application.
Inflammation during tooth movement
Inflammation characteristically displays the clinical signs of redness, heat, swelling, pain, and associated loss of function. It may be caused by a number of factors, including bacterial infection, or chemical or mechanical irritation. Histological examination reveals that acute inflammation is characterized by vasodilatation and is accompanied by increased
