Regulation of gene expression of tumour necrosis factor-alpha by protein kinase C in the rat dental follicle.

Tooth eruption requires alveolar bone resorption to form an eruption pathway. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) may increase bone resorption by promoting the recruitment of mononuclear cells to the dental follicle to form osteoclasts. Although the major osteoclast burst is seen early postnatally in the rat (day 3), the second round of minor osteoclastogenesis is around postnatal day 10. We have previously reported that TNF-alpha is expressed in the dental follicle of newborn rats with maximum expression at day 9. Such expression is enhanced by IL-1alpha in cultured dental follicle cells. In this report, regulation of TNF-alpha expression by protein kinase C (PKC) was studied both in vitro and in vivo. Incubating dental follicle cells with phorbolmyristate acetate (PMA), a PKC activator, significantly up-regulated TNF-alpha gene expression in a dosage-dependent manner. A PKC specific inhibitor, Gö 6983, abolished this PMA effect on up-regulation of TNF-alpha, but had no effect on IL-1alpha induced expression. TNF-alpha expression was significantly greater after treatment with a combination of PMA and IL-1alpha than in treatments with PMA or IL-1alpha alone, suggesting a synergistic effect on enhancing TNF-alpha expression. These gene expression results were confirmed at the protein level by immunostaining for TNF-alpha in the dental follicle cells. In vivo, injection of PMA into postnatal rats also increased TNF-alpha expression. Thus, PKC up-regulates TNF-alpha expression in dental follicle cells, as does IL-1alpha. However, they appear to utilize different pathways to regulate TNF-alpha expression.