HMGB1-Protein as a Possible Marker to Identify Side Effects in Periodontal Remodeling Following Mechanical Loading

Objectives: High-mobility-group-box-protein 1 (HMGB1) is released into the extracellular milieu by damaged PDL-cells and functions as an alarmin to mediate the inflammatory host response and regulate periodontal remodeling. Recent studies indicated that a fail regulation of released HMGB1 during periodontal remodeling can lead to an immune over reaction resulting in the destruction of dental tissues. Therefore, it was the aim of the present investigation to further analyze the distinguish role of HMGB1 within the periodontal remodeling process following orthodontic tooth movement. We hypothesized that, due to its immunological function, HMGB1 is capable to function as a diagnostic protein to identify negative side effects in orthodontic tooth movement.

Methods: HMGB1 expression by cultured human PDL-cells and of orthodontically treated rats was analyzed by means of immunocytochemistry/ELISA. The influence of HMGB1 secreted by PDL-cells on macrophage physiology was investigated by migration and osteoclastic differentiation assays. To transfer these findings to the clinical side, orthodontically treated patients were analyze for tissue HMGB1 expression within the crevicular fluid and correlated with excessive bone removal/root resorption.
Results: Induction of mechanical stress in vivo and in vitro resulted in enhanced HMGB1 protein expression and an intracellular translocation of HMGB1 in the initial phase of tissue repair. Migration and osteoclastic differentiation of human macrophages is regulated by PDL cell expressed HMGB1. Side effects in clinical orthodontic treatment by means of bone removal or root resorption was accompanied with an increase in crevicular fluid HMGB1 protein expression.

Conclusions: These data clearly point to a possible role of HMGB1 in periodontal tissue repair with an immune modulatory function when acting in concert with other cytokines in mechanical induced tissue remodeling. High levels of HMGB1 in crevicular fluid seem to be a possible marker to identify side effects of orthodontic treatment. These findings extend the basis for possible prevention and therapeutical intervention strategies for tissue damage that might occur in the course of orthodontic treatment.