4-Hexylresorcinol Administration Increases Dental Hard Tissue Formation and Incisor Eruption Rate in Rats

Dental hard tissue formation and bone turnover are required for tooth eruption. 4-Hexylresorcinol (4HR) accelerates tooth movement by increasing bone turnover in orthodontic treatment. This study aimed to evaluate the following: (1) the effect of 4HR application on the expression of proteins associated with tooth formation, and (2) the effect of 4HR application on mandibular incisor eruption rate in a rat model. Primary cultured pulp cells received either 4HR (1 to 100 µM) or solvent only; western blotting was performed for transforming growth factor-beta 1 (TGF-β1), bone morphogenic protein-2/4 (BMP-2/4), runt-related transcription factor 2 (Runx2), osterix (OSX), dentin sialophosphoprotein (DSPP), and parathyroid hormone-related protein receptor (PTHrP-R). In in vivo study, rats (15 males and 15 females) received either solvent or 0.128 mg/kg or 12.8 mg/kg of 4HR via subcutaneous injection; mandibular incisor eruption rate was subsequently recorded. Immunohistochemical staining and western blotting for TGF-β1, BMP-2/4, Runx2, OSX, DSPP, and PTHrP-R were performed in the mandibular tissue samples. 4HR administration was found to increase TGF-β1, BMP-2/4, Runx2, OSX, DSPP, and PTHrP-R expression in both cell culture and tissue samples. Immunohistochemical staining of some markers showed site-specific expression, thereby indicating programmed differentiation of odontoblasts and ameloblasts. The eruption rate was significantly higher in the 12.8 mg/kg 4HR-administered group than in the untreated control (p = 0.001 and 0.010 for males and females, respectively). Collectively, 4HR administration increased the expression of markers related to dental hard tissue formation and accelerated the eruption rate of incisors in rats.