Loss of Nucleoside Transporter ENT1 Slows Incisor Eruption in Mice

Objectives: Equilibrative nucleoside transporter 1 (ENT1) transfers nucleosides, such as adenosine, across plasma membranes. We reported previously that mice lacking ENT1 (ENT1-KO) exhibit ectopic calcification of spinal tissues, sternocostal articulations, and the mandibular symphysis. The current study assessed dental and periodontal tissues in ENT1-KO mice.
Methods: Heads from ENT1-KO and wild-type (WT) mice at 3 and 6 months-of-age were scanned using micro-CT to evaluate the morphology and densities of teeth and adjacent tissues. Representative samples were decalcified and processed for histological assessment. Rates of eruption of mandibular incisors were measured at 2 months-of-age using a tooth notch assay. Connective tissue fibroblasts isolated from ENT1-KO and WT mice were assayed in vitro for differences in cell adhesion and cell-mediated matrix contraction.
Results: No hypercementosis or ectopic calcification of the periodontal ligament was detected in ENT1-KO mice. Micro-CT analysis revealed generally normal dental morphology in mice lacking ENT1. However, mineralization of enamel was greater toward the apical end of ENT1-KO incisors. Moreover, pulp chambers of ENT1-KO incisors were smaller in diameter than those of WT mice. These differences are consistent with a slower rate of eruption in ENT1-KO mice. This was confirmed by measurement of eruption rates in vivo (0.22 ± 0.02 and 0.31 ± 0.02 mm/day in ENT1-KO and WT mice, respectively, n = 6, p = 0.01). Although no difference was detected between adhesion of ENT1-KO and WT fibroblasts in vitro, the ability of ENT1-KO fibroblasts to contract collagen gels was significantly less than that of WT cells.
Conclusions: These results demonstrate that loss of the adenosine transporter ENT1 slows the rate of incisor eruption. This effect may be mediated by a defect in the ability of ENT1-KO fibroblasts to generate tension. These findings are consistent with a role for adenosine in the regulation of tooth eruption.