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This study investigated whether orthodontic force influencesthe production of osteoprotegerin (OPG) andreceptor activator of nuclear factor-kappa B ligand (RANKL)in vivo, both of which are affected by cortical activation. Mechanical force was applied to the maxillary premolars oforthodontic patients by fitting the transpalatal arch prior tocortical activation of the gingival tissue. Gingival crevicularfluid (GCF) samples were then collected from each patientusing paper strips before and after 1, 3, 7 or 14 days oftreatment. The OPG and RANKL levels in the GCF weredetermined by enzyme-linked immunosorbent assays. Thelevels of OPG were significantly increased after 1 day offitting the appliance and decreased to basal levels at 3 daysafter fitting. In contrast, the RANKL levels were dramaticallydecreased at 1 day after fitting, but recovered to thoseof the untreated control at 3 days after the force application. The force-mediated changes in the OPG and RANKL levelsof the GCF were unaffected by cortical activation duringthese experimental periods. Collectively, these results suggestthat an acute and severe change between the OPG andRANKL levels plays an important role in stimulating thecellular responses required for alveolar bone remodeling byorthodontic treatment.

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