Orthodontic Force Induces Systemic Inflammatory Monocyte Responses

Periodontal inflammation and alveolar bone remodeling during orthodontic tooth movement are considered regional reactions. However, how systemic immune responses are involved in this regional reaction remains unclear. In this study, we explored the systemic effects of orthodontic force by focusing on the mononuclear phagocyte system. Flow cytometric analysis showed that the percentage of inflammatory monocytes, in peripheral blood and in the monocyte reservoir spleen, decreased on days 1 and 3 and then recovered on day 7 after force application. Along with the systemic decrease of inflammatory monocyte percentage, the number of tartrate-resistant acid phosphatase-positive osteoclasts increased in the compression side of the periodontal tissue during orthodontic tooth movement. Systemic transfusion of enhanced green fluorescent protein-labeled inflammatory monocytes showed recruitment of these monocytes to the orthodontic force compression side of periodontal tissues. These monocytes were colocalized with tartrate-resistant acid phosphatase-positive osteoclasts. In vivo and in vitro experiments showed that orthodontic force could upregulate the expression of pivotal monocyte chemokine monocyte chemotactic protein 1 in periodontal tissues or cultured periodontal ligament cells, which may contribute to monocyte recruitment to regional sites. These data suggest that orthodontic force induces systemic immune responses related to inflammatory monocytes and that systemic inflammatory monocytes can be recruited to periodontal tissues by orthodontic force stimulus.