Regulation of high mobility group box protein 1 expression following mechanical loading by orthodontic forces in vitro and in vivo.

SUMMARY
INTRODUCTION: The chromatin-binding protein high mobility group box protein 1 (HMGB1) can be released into the extracellular milieu by necrotic and damaged cells and functions as an alarmin that is recognized by the innate immune system to initiate and modulate tissue repair. However, little is known about the function of HMGB1 within orthodontic tooth movement. Therefore, it was the aim of the present study to investigate HMGB1 expression by periodontal ligament (PDL) cells challenged by mechanical loading similar to force levels being applied in orthodontic treatment in vitro and to transfer these findings to an in vivo microenvironment in an animal model of tooth movement in rats. In addition, we addressed the question of whether the regulation of HMGB1 expression is modulated in a time-dependent manner in zones of compressive forces. METHODS AND
RESULTS: Protein analysis revealed a basal HMGB1 expression in PDL cell cultures and an increased expression when orthodontic forces were applied. In a rat model of tooth movement including 25 animals that received orthodontic tooth movement for 3, 6, 9, and 12 days, HMGB1 protein expression was demonstrated to be regulated in a time-dependent manner as determined by means of immunohistochemistry and histomorphometrical analyses.
CONCLUSION: These data indicate a potential role for HMGB1 protein originating from PDL cells in the regulation of orthodontic tooth movement and the periodontal remodelling process by modifying the local microenvironment.