Inflammatory responses of immune cells and osteoblasts in orthodontically-induced bone remodelling and root resorption: in vitro and in vivo studies

Orthodontic tooth movement is achieved by remodelling of the surrounding bone in response to the application of appropriate compressive force (CF) to the tooth. Considerable evidence supports the roles of immune cells of the periodontal ligament (PDL) and dental pulp during the remodelling process. One essential mechanism for initiation of this process is the inflammatory response to the application of force by immune cells, which migrate from the capillaries of the PDL. Osteoblasts are also involved in inflammation and osteoclastogenesis in the PDL during alveolar bone remodelling. If excessive CF is applied, root resorption may be an unwanted complication of the bone remodelling process. The role of the immune cells in orthodontically-induced root resorption is poorly understood and little is known about the response of osteoblasts to compressive force (CF). Improved understanding of the molecular and cellular events which regulate bone formation and bone resorption in orthodontic tooth movement is fundamental to the development of clinical guidelines offering greater precision in determining optimal CF to achieve tooth movement while avoiding the untoward complication of root resorption induced by the application of excessive force. The aim of the in vivo and in vitro studies on which this thesis is based was to investigate the responses to CF of immune cells and osteoblasts derived from human alveolar bone (HOBs). In Paper I, an in vivo study in rats, extensive root resorption was created by the application of two-cycle orthodontic forces. Resorption was observed in the compression zone of the teeth being moved. Recruitment of immune cells, including monocytes, macrophages and MHC class II Ia-expressing cells, but not granulocytes or lymphocytes, was confined mainly to the compressed PDL, whereas the dental pulp was not markedly affected. The results suggest that extensive root resorption causes only minimal pulpal changes. In the in vitro studies (Papers II and III), HOBs were used to study the initial effects of varying magnitudes of CF on cell viability, proliferation, apoptosis and the expression of molecules involved in inflammation and the bone remodelling process. The results show that the main effect of CF is to inhibit cell-proliferative activity, without a corresponding increase in cell apoptosis. CF induces the expression of inflammatory mediators IL-6 and CXCL8 in a force-dependent manner. Furthermore, initial application of CF on HOBs can simultaneously affect the expression of markers related to both osteogenesis (initial stage: ALP and Col 1) and osteoclastogenesis (RANKL and OPG). The results of the studies provide evidence of the potentially pivotal roles of both the immune cells and the osteoblasts of the PDL in extensive root resorption induced by orthodontic tooth movement