A critical cellular event in tooth eruption is the formation of osteoclasts that are needed for bone resorption to form an eruption pathway. To analyze molecular regulation of osteoclast formation and activation, we examined the expression of osteoprotegerin (OPG), an inhibitor of osteoclast formation. In vivo, the gene expression of OPG is reduced in the dental follicle of the first mandibular molar of the rat at day 3 post-natally and in the mouse at day 5. This correlates with the days of maximal mononuclear cell influx and osteoclast numbers in the rat and mouse. Thus, inhibition of OPG gene expression on these days might allow osteoclasts to be formed and/or activated. In vitro studies demonstrated that both colony-stimulating factor-1 and parathyroid hormone-related protein reduced OPG gene expression in follicle cells, suggesting that these are candidate molecules for the in vivo inhibition of OPG expression. Osteoclast differentiation factor (ODF) immunolocalizes to the alveolar bone stromal cells adjacent to the follicle, whereby it might act to stimulate fusion of the mononuclear cells in the follicle.

The monocyte chemotactic protein-1 (MCP-1) gene is expressed in the dental follicle, a loose connective tissue sac that must be present for eruption to occur. The role of MCP-1 may be to recruit mononuclear cells (monocytes) to the dental follicle, where these cells, in turn, fuse to form osteoclasts to resorb alveolar bone for the formation of an eruption pathway. Thus, it was the aim of this study to determine if MCP-1 is secreted by dental follicle cells in culture and if its secretion is enhanced by potential tooth eruption molecules. Western blotting and a two-site capture enzyme-linked immunoabsorbent assay demonstrated that MCP-1 was synthesized and secreted into the medium by the follicle cells. Incubation of the cells with either transforming growth factor-beta one (TGF-beta 1) or interleukin-one alpha (IL-1 alpha) enhanced the secretion of MCP-1 by the cells. Measurement of the chemotactic ability of the conditioned medium to attract mouse monocytes demonstrated that the chemotaxis of the medium was increased if the cells had previously been incubated in IL-1 alpha, although there appears to be a threshold concentration of MCP-1 above which chemotaxis is not enhanced. These combined results suggest that the critical initial cellular event of tooth eruption, an influx of mononuclear cells into the dental follicle at an early post-natal age, may be initiated by the secretion of MCP-1 by the dental follicle cells.

No abstract

Tooth eruption requires alveolar bone resorption and the presence of the dental follicle, a loose connective tissue sac that surrounds each tooth. This bone resorption involves the follicle in that mononuclear cells enter the follicle to form osteoclasts which resorb bone to form the eruption pathway. In the rat first mandibular molar, probable eruption genes, CSF-1, c-fos, NFkappaB and MCP-1, are expressed maximally in the dental follicle at day 3 postnatally. This correlates with the time of peak influx of mononuclear cells into the follicle. In the mouse, the first peak influx of mononuclear cells into the first mandibular molar is at day 5 postnatally, and this study demonstrates that all four of the above resorption molecules are maximally expressed at this time in the dental follicle. Thus, this work suggests that these molecules may play a role in the cellular events of eruption (mononuclear cell influx and osteoclast formation) in the mouse molar at day 5 postnatally just as they do at day 3 in the rat molar. These results provide a standard for future studies on eruption in the mouse molar and extends the number of species in which putative eruption molecules are expressed at a critical time of eruption.