The IGF-I/IGFBP-3 system in gingival crevicular fluid and dependence on application of fixed force

Background: During application of orthodontic force on the tooth, various molecular parameters associated with tissue remodeling are changed. IGF-I is a regulatory protein produced during periodontal regeneration. IGF binding proteins- 3 (IGFBP-3), a specific IGF-I binding protein, is the major regulatory factor of IGF-I activity. Objectives: We tested the hypothesis that changes in the IGF-I/IGFBP-3 system occur during fixed force application to the tooth and that these changes are detectable in the gingival crevicular fluid (GCF). Methods: IGFBP-3 and IGF-I secretion into gingival crevicular fluid (GCF) was analyzed by Western blotting and immunoradiometric assay (IRMA), respectively, in GCF of 6 healthy subjects just prior to and during orthodontics treatment using fixed appliances. Results: We observed a significant time-dependent decrease of IGFBP-3 content in GCF during orthodontic treatment (4 h and 10 days). Reduction in levels of intact, glycosylated 47 kDa form of IGFBP-3 was associated with its degradation and the appearance of intermediate breakdown products. IGF-I levels were significantly increased 4 h after application of orthodontic force, while they were significantly reduced 10 days after the start of treatment. Conclusions: IGFBP-3 secretion into GCF and its molecular structure are modified by the fixed force of orthodontic treatment. Alterations in IGFBP-3 appear to be unrelated to the binding to IGF-I, suggesting an IGF-independent role of this binding protein in tooth movement.