Tooth eruption requires alveolar bone resorption that is regulated by the dental follicle. This is reflected by the fact that failures of eruption often can be traced to either osteoclast deficiencies or to dental follicle abnormalities. To achieve maximal osteoclastogenesis and subsequent alveolar bone resorption for eruption, we have hypothesized that a reduction in gene expression of osteoprotegerin (OPG) in the follicle of the first mandibular molar of the rat at Day 3 is needed. To determine if OPG affects eruption, postnatal rats were injected with varying concentrations of OPG from Days 1-9 postnatally. Such studies indicated that the eruption time of the first mandibular molar was significantly delayed by 1 day or more as a result of OPG injection. Injection of phorbolmyristate acetate (PMA), an activator of protein kinase C (PKC) that in turn upregulates OPG expression, also delayed eruption by 1 day. PMA was only injected from Days 1-4 such that PKC-alpha would be increased and activated. Previous studies had shown that PKC-alpha gene expression is downregulated at the time (Day 3) that OPG expression is downregulated. In this study, using reverse transcription polymerase chain reaction techniques to examine OPG gene expression showed that PMA injection increased OPG gene expression in the dental follicle at Day 3 as compared to the controls. Thus, either injecting OPG or enhancing its expression in the follicle at Day 3 by injecting PMA delays the time of tooth eruption. Consequently, regulation of OPG production by the dental follicle likely affects the alveolar bone resorption needed for tooth eruption.